SCN5A_HUMAN
ID SCN5A_HUMAN Reviewed; 2016 AA.
AC Q14524; A5H1P8; A6N922; A6N923; B2RTU0; E7ET19; E9PEF3; E9PEK2; E9PFW7;
AC Q59H93; Q75RX9; Q75RY0; Q86UR3; Q8IZC9; Q96J69;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Sodium channel protein type 5 subunit alpha;
DE AltName: Full=Sodium channel protein cardiac muscle subunit alpha;
DE AltName: Full=Sodium channel protein type V subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.5;
DE AltName: Full=hH1 {ECO:0000303|PubMed:1309946};
GN Name=SCN5A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP VARIANTS ARG-552 AND GLN-1027.
RC TISSUE=Heart;
RX PubMed=1309946; DOI=10.1073/pnas.89.2.554;
RA Gellens M.E., George A.L. Jr., Chen L.Q., Chahine M., Horn R., Barchi R.L.,
RA Kallen R.G.;
RT "Primary structure and functional expression of the human cardiac
RT tetrodotoxin-insensitive voltage-dependent sodium channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:554-558(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND VARIANT
RP ARG-552.
RC TISSUE=Jejunal smooth muscle;
RX PubMed=12358675; DOI=10.1046/j.1365-2982.2002.00348.x;
RA Ou Y., Gibbons S.J., Miller S.M., Strege P.R., Rich A., Distad M.A.,
RA Ackerman M.J., Rae J.L., Szurszewski J.H., Farrugia G.;
RT "SCN5A is expressed in human jejunal circular smooth muscle cells.";
RL Neurogastroenterol. Motil. 14:477-486(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ARG-558 AND TYR-1103.
RX PubMed=14500339; DOI=10.1161/01.res.0000096652.14509.96;
RA Makielski J.C., Ye B., Valdivia C.R., Pagel M.D., Pu J., Tester D.J.,
RA Ackerman M.J.;
RT "A ubiquitous splice variant and a common polymorphism affect heterologous
RT expression of recombinant human SCN5A heart sodium channels.";
RL Circ. Res. 93:821-828(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-558, AND
RP CHARACTERIZATION OF VARIANT LQT3 LEU-1766.
RX PubMed=12454206; DOI=10.1152/physiolgenomics.00117.2002;
RA Ye B., Valdivia C.R., Ackerman M.J., Makielski J.C.;
RT "A common human SCN5A polymorphism modifies expression of an arrhythmia
RT causing mutation.";
RL Physiol. Genomics 12:187-193(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), AND VARIANT THR-1498.
RX PubMed=16115203; DOI=10.1111/j.1460-9568.2005.04280.x;
RA Ou S.-W., Kameyama A., Hao L.-Y., Horiuchi M., Minobe E., Wang W.-Y.,
RA Makita N., Kameyama M.;
RT "Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are
RT encoded by new variants of Nav1.5/SCN5A.";
RL Eur. J. Neurosci. 22:793-801(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), AND VARIANTS LEU-336 AND
RP GLN-1027.
RA Wang J., Ou S.-W., Wang Y.-J., Zong Z.-H.;
RT "Cloning, distribution and analysis of the new exon encoding Nav1.5 channel
RT in brain tissues.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 34:255-259(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ARG-558.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 422-2016 (ISOFORMS 3/6).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP INTERACTION WITH NEDD4L, UBIQUITINATION, AND MUTAGENESIS OF TYR-1977 AND
RP VAL-1980.
RX PubMed=15217910; DOI=10.1161/01.res.0000136816.05109.89;
RA van Bemmelen M.X., Rougier J.-S., Gavillet B., Apotheloz F., Daidie D.,
RA Tateyama M., Rivolta I., Thomas M.A., Kass R.S., Staub O., Abriel H.;
RT "Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2
RT mediated ubiquitination.";
RL Circ. Res. 95:284-291(2004).
RN [12]
RP INTERACTION WITH NEDD4; NEDD4L AND WWP2, UBIQUITINATION, AND MUTAGENESIS OF
RP PRO-1974; PRO-1975; SER-1976; TYR-1977; ASP-1978; SER-1979 AND VAL-1980.
RX PubMed=15548568; DOI=10.1152/ajpcell.00460.2004;
RA Rougier J.-S., van Bemmelen M.X., Bruce M.C., Jespersen T., Gavillet B.,
RA Apotheloz F., Cordonier S., Staub O., Rotin D., Abriel H.;
RT "Molecular determinants of voltage-gated sodium channel regulation by the
RT Nedd4/Nedd4-like proteins.";
RL Am. J. Physiol. 288:C692-C701(2005).
RN [13]
RP MUTAGENESIS OF GLN-1476.
RX PubMed=16054936; DOI=10.1016/s0140-6736(05)66786-4;
RA Dichgans M., Freilinger T., Eckstein G., Babini E., Lorenz-Depiereux B.,
RA Biskup S., Ferrari M.D., Herzog J., van den Maagdenberg A.M.J.M., Pusch M.,
RA Strom T.M.;
RT "Mutation in the neuronal voltage-gated sodium channel SCN1A in familial
RT hemiplegic migraine.";
RL Lancet 366:371-377(2005).
RN [14]
RP INTERACTION WITH GPD1L, AND PHOSPHORYLATION AT SER-1503 BY PKC.
RX PubMed=19666841; DOI=10.1152/ajpheart.00513.2009;
RA Valdivia C.R., Ueda K., Ackerman M.J., Makielski J.C.;
RT "GPD1L links redox state to cardiac excitability by PKC-dependent
RT phosphorylation of the sodium channel SCN5A.";
RL Am. J. Physiol. 297:H1446-H1452(2009).
RN [15]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY (ISOFORM 4).
RX PubMed=19376164; DOI=10.1016/j.neures.2009.04.003;
RA Wang J., Ou S.-W., Wang Y.-J., Kameyama M., Kameyama A., Zong Z.-H.;
RT "Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain.";
RL Neurosci. Res. 64:339-347(2009).
RN [16]
RP REVIEW ON VARIANTS.
RX PubMed=19027780; DOI=10.1016/j.pbiomolbio.2008.10.005;
RA Zimmer T., Surber R.;
RT "SCN5A channelopathies - An update on mutations and mechanisms.";
RL Prog. Biophys. Mol. Biol. 98:120-136(2008).
RN [17]
RP ALTERNATIVE SPLICING.
RX PubMed=20398673; DOI=10.1016/j.yjmcc.2010.04.004;
RA Schroeter A., Walzik S., Blechschmidt S., Haufe V., Benndorf K., Zimmer T.;
RT "Structure and function of splice variants of the cardiac voltage-gated
RT sodium channel Na(v)1.5.";
RL J. Mol. Cell. Cardiol. 49:16-24(2010).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21447824; DOI=10.1161/circgenetics.110.959130;
RA Kattygnarath D., Maugenre S., Neyroud N., Balse E., Ichai C., Denjoy I.,
RA Dilanian G., Martins R.P., Fressart V., Berthet M., Schott J.J.,
RA Leenhardt A., Probst V., Le Marec H., Hainque B., Coulombe A., Hatem S.N.,
RA Guicheney P.;
RT "MOG1: a new susceptibility gene for Brugada syndrome.";
RL Circ. Cardiovasc. Genet. 4:261-268(2011).
RN [19]
RP INTERACTION WITH FGF13.
RX PubMed=21817159; DOI=10.1161/circresaha.111.247957;
RA Wang C., Hennessey J.A., Kirkton R.D., Wang C., Graham V., Puranam R.S.,
RA Rosenberg P.B., Bursac N., Pitt G.S.;
RT "Fibroblast growth factor homologous factor 13 regulates Na+ channels and
RT conduction velocity in murine hearts.";
RL Circ. Res. 109:775-782(2011).
RN [20]
RP METHYLATION AT ARG-513; ARG-526 AND ARG-680.
RX PubMed=21726068; DOI=10.1021/pr200339n;
RA Beltran-Alvarez P., Pagans S., Brugada R.;
RT "The cardiac sodium channel is post-translationally modified by arginine
RT methylation.";
RL J. Proteome Res. 10:3712-3719(2011).
RN [21]
RP PHOSPHORYLATION AT SER-36; THR-38; SER-457; SER-460; SER-483; SER-484;
RP SER-497; SER-510; SER-571; SER-664 AND SER-667.
RX PubMed=23092124; DOI=10.1021/pr300702c;
RA Marionneau C., Lichti C.F., Lindenbaum P., Charpentier F., Nerbonne J.M.,
RA Townsend R.R., Merot J.;
RT "Mass spectrometry-based identification of native cardiac Nav1.5 channel
RT alpha subunit phosphorylation sites.";
RL J. Proteome Res. 11:5994-6007(2012).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ATRST1
RP ASN-1275; VARIANT ASN-1275 BRGDA1; VARIANT ASN-1275 CMD1E; VARIANT PFHB1A
RP ASN-1275 AND VARIANT BRGDA1 ARG-1743.
RX PubMed=23420830; DOI=10.1161/circep.111.000206;
RA Chakrabarti S., Wu X., Yang Z., Wu L., Yong S.L., Zhang C., Hu K.,
RA Wang Q.K., Chen Q.;
RT "MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada
RT syndrome and sick sinus syndrome.";
RL Circ. Arrhythm. Electrophysiol. 6:392-401(2013).
RN [23]
RP MUTAGENESIS OF ASP-1610.
RX PubMed=24898004; DOI=10.1124/mol.114.092338;
RA Xiao Y., Blumenthal K., Cummins T.R.;
RT "Gating-pore currents demonstrate selective and specific modulation of
RT individual sodium channel voltage-sensors by biological toxins.";
RL Mol. Pharmacol. 86:159-167(2014).
RN [24]
RP MUTAGENESIS OF ASP-1610 AND LYS-1614, AND SUBUNIT.
RX PubMed=26721415; DOI=10.1016/j.toxicon.2015.12.009;
RA Tao H., Chen X., Lu M., Wu Y., Deng M., Zeng X., Liu Z., Liang S.;
RT "Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the
RT fast inactivation of voltage-gated sodium channels.";
RL Toxicon 111:13-21(2016).
RN [25]
RP STRUCTURE BY NMR OF 1773-1865, FUNCTION, SUBCELLULAR LOCATION, RESPONSE TO
RP CALCIUM, AND MUTAGENESIS OF 1802-ASP--GLU-1804.
RX PubMed=19074138; DOI=10.1074/jbc.m807747200;
RA Chagot B., Potet F., Balser J.R., Chazin W.J.;
RT "Solution NMR structure of the C-terminal EF-hand domain of human cardiac
RT sodium channel NaV1.5.";
RL J. Biol. Chem. 284:6436-6445(2009).
RN [26]
RP STRUCTURE BY NMR OF 1901-1927 IN COMPLEX WITH CALM, AND INTERACTION WITH
RP CALM.
RX PubMed=21167176; DOI=10.1016/j.jmb.2010.11.046;
RA Chagot B., Chazin W.J.;
RT "Solution NMR structure of Apo-calmodulin in complex with the IQ motif of
RT human cardiac sodium channel NaV1.5.";
RL J. Mol. Biol. 406:106-119(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1773-1940 IN COMPLEX WITH FGF13
RP AND CALMODULIN.
RX PubMed=22705208; DOI=10.1016/j.str.2012.05.001;
RA Wang C., Chung B.C., Yan H., Lee S.Y., Pitt G.S.;
RT "Crystal structure of the ternary complex of a NaV C-terminal domain, a
RT fibroblast growth factor homologous factor, and calmodulin.";
RL Structure 20:1167-1176(2012).
RN [28] {ECO:0007744|PDB:4OVN}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1773-1929, FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH CALMODULIN.
RX PubMed=25370050; DOI=10.1038/ncomms6126;
RA Gabelli S.B., Boto A., Kuhns V.H., Bianchet M.A., Farinelli F.,
RA Aripirala S., Yoder J., Jakoncic J., Tomaselli G.F., Amzel L.M.;
RT "Regulation of the NaV1.5 cytoplasmic domain by calmodulin.";
RL Nat. Commun. 5:5126-5126(2014).
RN [29]
RP VARIANTS LQT3.
RX PubMed=7889574; DOI=10.1016/0092-8674(95)90359-3;
RA Wang Q., Shen J., Splawski I., Atkinson D., Li Z., Robinson J.L.,
RA Moss A.J., Towbin J.A., Keating M.T.;
RT "SCN5A mutations associated with an inherited cardiac arrhythmia, long QT
RT syndrome.";
RL Cell 80:805-811(1995).
RN [30]
RP VARIANTS LQT3.
RX PubMed=8541846; DOI=10.1093/hmg/4.9.1603;
RA Wang Q., Shen J., Li Z., Timothy K.W., Vincent G.M., Priori S.G.,
RA Schwartz P.J., Keating M.T.;
RT "Cardiac sodium channel mutations in patients with long QT syndrome, an
RT inherited cardiac arrhythmia.";
RL Hum. Mol. Genet. 4:1603-1607(1995).
RN [31]
RP VARIANT LQT3 1505-LYS--GLN-1507 DEL.
RX PubMed=7651517; DOI=10.1038/376683a0;
RA Bennett P.B., Yazawa K., Makita N., George A.L. Jr.;
RT "Molecular mechanism for an inherited cardiac arrhythmia.";
RL Nature 376:683-685(1995).
RN [32]
RP VARIANT LQT3 GLY-1790.
RX PubMed=9686753; DOI=10.1161/01.res.83.2.141;
RA An R.H., Wang X.L., Kerem B., Benhorin J., Medina A., Goldmit M.,
RA Kass R.S.;
RT "Novel LQT-3 mutation affects Na+ channel activity through interactions
RT between alpha- and beta1-subunits.";
RL Circ. Res. 83:141-146(1998).
RN [33]
RP VARIANT LQT3 GLN-1623.
RX PubMed=9506831; DOI=10.1016/s0014-5793(98)00033-7;
RA Makita N., Shirai N., Nagashima M., Matsuoka R., Yamada Y., Tohse N.,
RA Kitabatake A.;
RT "A de novo missense mutation of human cardiac Na(+) channel exhibiting
RT novel molecular mechanisms of long QT syndrome.";
RL FEBS Lett. 423:5-9(1998).
RN [34]
RP VARIANT LQT3 GLY-1839.
RX PubMed=10627139;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<72::aid-humu19>3.0.co;2-t;
RA Benhorin J., Goldmit M., Maccluer J.W., Blangero J., Goffen R.,
RA Leibovitch A., Rahat A., Wang Q., Medina A., Towbin J.A., Kerem B.;
RT "Identification of a new SCN5A mutation, D1840G, associated with the long
RT QT syndrome.";
RL Hum. Mutat. 12:72-72(1998).
RN [35]
RP VARIANT LQT3 GLN-1623.
RA Yamagishi H., Furutani M., Kamisago M., Morikawa Y., Kojima Y., Hino Y.,
RA Furutani Y., Kimura M., Imamura S., Takao A., Momma K., Matsuoka R.;
RT "A De Novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl
RT with sporadic long QT syndrome.";
RL Hum. Mutat. 12:481-481(1998).
RN [36]
RP VARIANTS BRGDA1 TRP-1232 AND MET-1620.
RX PubMed=9521325; DOI=10.1038/32675;
RA Chen Q., Kirsch G.E., Zhang D., Brugada R., Brugada J., Brugada P.,
RA Potenza D., Moya A., Borggrefe M., Breithardt G., Ortiz-Lopez R., Wang Z.,
RA Antzelevitch C., O'Brien R.E., Schulze-Bahr E., Keating M.T., Towbin J.A.,
RA Wang Q.;
RT "Genetic basis and molecular mechanism for idiopathic ventricular
RT fibrillation.";
RL Nature 392:293-296(1998).
RN [37]
RP VARIANTS LQT3 MET-1304 AND MET-1645, AND VARIANT ASN-1500.
RX PubMed=10508990;
RX DOI=10.1002/(sici)1096-8628(19991029)86:5<470::aid-ajmg13>3.0.co;2-y;
RA Wattanasirichaigoon D., Vesely M.R., Duggal P., Levine J.C., Blume E.D.,
RA Wolff G.S., Edwards S.B., Beggs A.H.;
RT "Sodium channel abnormalities are infrequent in patients with long QT
RT syndrome: identification of two novel SCN5A mutations.";
RL Am. J. Med. Genet. 86:470-476(1999).
RN [38]
RP CHARACTERIZATION OF VARIANTS BRGDA1 TRP-1512 AND THR-1924.
RX PubMed=10690282; DOI=10.1016/s0008-6363(99)00350-8;
RA Rook M.B., Bezzina Alshinawi C., Groenewegen W.A., van Gelder I.C.,
RA van Ginneken A.C.G., Jongsma H.J., Mannens M.M.A.M., Wilde A.A.M.;
RT "Human SCN5A gene mutations alter cardiac sodium channel kinetics and are
RT associated with the Brugada syndrome.";
RL Cardiovasc. Res. 44:507-517(1999).
RN [39]
RP VARIANT LQT3 LYS-1784.
RX PubMed=10377081; DOI=10.1161/01.cir.99.24.3165;
RA Wei J., Wang D.W., Alings M., Fish F., Wathen M., Roden D.M.,
RA George A.L. Jr.;
RT "Congenital long-QT syndrome caused by a novel mutation in a conserved
RT acidic domain of the cardiac Na+ channel.";
RL Circulation 99:3165-3171(1999).
RN [40]
RP CHARACTERIZATION OF VARIANT BRGDA1 MET-1620.
RX PubMed=10532948; DOI=10.1161/01.res.85.9.803;
RA Dumaine R., Towbin J.A., Brugada P., Vatta M., Nesterenko D.V.,
RA Nesterenko V.V., Brugada J., Brugada R., Antzelevitch C.;
RT "Ionic mechanisms responsible for the electrocardiographic phenotype of the
RT Brugada syndrome are temperature dependent.";
RL Circ. Res. 85:803-809(1999).
RN [41]
RP CHARACTERIZATION OF VARIANT LQT3/BRGDA1 ASP-1795 INS.
RX PubMed=10590249; DOI=10.1161/01.res.85.12.1206;
RA Bezzina C.R., Veldkamp M.W., van Den Berg M.P., Postma A.V., Rook M.B.,
RA Viersma J.-W., van Langen I.M., Tan-Sindhunata G., Bink-Boelkens M.T.E.,
RA van Der Hout A.H., Mannens M.M.A.M., Wilde A.A.M.;
RT "A single Na(+) channel mutation causing both long-QT and Brugada
RT syndromes.";
RL Circ. Res. 85:1206-1213(1999).
RN [42]
RP DISEASE.
RX PubMed=10471492; DOI=10.1038/12618;
RA Schott J.-J., Alshinawi C., Kyndt F., Probst V., Hoorntje T.M.,
RA Hulsbeek M., Wilde A.A.M., Escande D., Mannens M.M.A.M., Le Marec H.;
RT "Cardiac conduction defects associate with mutations in SCN5A.";
RL Nat. Genet. 23:20-21(1999).
RN [43]
RP CHARACTERIZATION OF VARIANT BRGDA1 MET-1620.
RX PubMed=10618304; DOI=10.1161/01.cir.101.1.54;
RA Makita N., Shirai N., Wang D.W., Sasaki K., George A.L. Jr., Kanno M.,
RA Kitabatake A.;
RT "Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by
RT beta(1)-subunit.";
RL Circulation 101:54-60(2000).
RN [44]
RP VARIANTS LQT3 ASN-1114; VAL-1501; LEU-1623 AND HIS-1644, AND VARIANT
RP ASN-1787.
RX PubMed=10973849; DOI=10.1161/01.cir.102.10.1178;
RA Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G.,
RA Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M.,
RA Keating M.T.;
RT "Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A,
RT KCNE1, and KCNE2.";
RL Circulation 102:1178-1185(2000).
RN [45]
RP VARIANT VF1 LEU-1710.
RX PubMed=10940383; DOI=10.1016/s0014-5793(00)01875-5;
RA Akai J., Makita N., Sakurada H., Shirai N., Ueda K., Kitabatake A.,
RA Nakazawa K., Kimura A., Hiraoka M.;
RT "A novel SCN5A mutation associated with idiopathic ventricular fibrillation
RT without typical ECG findings of Brugada syndrome.";
RL FEBS Lett. 479:29-34(2000).
RN [46]
RP VARIANT LQT3 ASN-941.
RX PubMed=10911008; DOI=10.1056/nejm200007273430405;
RA Schwartz P.J., Priori S.G., Dumaine R., Napolitano C., Antzelevitch C.,
RA Stramba-Badiale M., Richard T.A., Berti M.R., Bloise R.;
RT "A molecular link between the sudden infant death syndrome and the long-QT
RT syndrome.";
RL N. Engl. J. Med. 343:262-267(2000).
RN [47]
RP VARIANT LQT3 LYS-1295, AND CHARACTERIZATION OF VARIANT LQT3 LYS-1295.
RX PubMed=11304498; DOI=10.1161/hh0701.089668;
RA Abriel H., Cabo C., Wehrens X.H., Rivolta I., Motoike H.K., Memmi M.,
RA Napolitano C., Priori S.G., Kass R.S.;
RT "Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in
RT the cardiac Na(+) channel.";
RL Circ. Res. 88:740-745(2001).
RN [48]
RP CHARACTERIZATION OF VARIANT LQT3 CYS-1795, AND CHARACTERIZATION OF VARIANT
RP BRGDA1 HIS-1795.
RX PubMed=11410597; DOI=10.1074/jbc.m104471200;
RA Rivolta I., Abriel H., Tateyama M., Liu H., Memmi M., Vardas P.,
RA Napolitano C., Priori S.G., Kass R.S.;
RT "Inherited Brugada and long QT-3 syndrome mutations of a single residue of
RT the cardiac sodium channel confer distinct channel and clinical
RT phenotypes.";
RL J. Biol. Chem. 276:30623-30630(2001).
RN [49]
RP VARIANT SSS1/BRGDA1 ARG-1408.
RX PubMed=11748104; DOI=10.1161/hc5001.100834;
RA Kyndt F., Probst V., Potet F., Demolombe S., Chevallier J.-C., Baro I.,
RA Moisan J.-P., Boisseau P., Schott J.-J., Escande D., Le Marec H.;
RT "Novel SCN5A mutation leading either to isolated cardiac conduction defect
RT or Brugada syndrome in a large French family.";
RL Circulation 104:3081-3086(2001).
RN [50]
RP CHARACTERIZATION OF VARIANTS LQT3 SER-997 AND HIS-1826.
RX PubMed=11710892; DOI=10.1001/jama.286.18.2264;
RA Ackerman M.J., Siu B.L., Sturner W.Q., Tester D.J., Valdivia C.R.,
RA Makielski J.C., Towbin J.A.;
RT "Postmortem molecular analysis of SCN5A defects in sudden infant death
RT syndrome.";
RL JAMA 286:2264-2269(2001).
RN [51]
RP CHARACTERIZATION OF VARIANT PFHB1A CYS-514.
RX PubMed=11234013; DOI=10.1038/35059090;
RA Tan H.L., Bink-Boelkens M.T.E., Bezzina C.R., Viswanathan P.C.,
RA Beaufort-Krol G.C.M., van Tintelen P.J., van den Berg M.P., Wilde A.A.M.,
RA Balser J.R.;
RT "A sodium-channel mutation causes isolated cardiac conduction disease.";
RL Nature 409:1043-1047(2001).
RN [52]
RP VARIANTS BRGDA1 LYS-161; CYS-367; LYS-369; ARG-752; LYS-1225; VAL-1319;
RP ILE-1382; LEU-1405; ARG-1406; LYS-1479 DEL; SER-1502; TRP-1512; GLU-1743
RP AND THR-1924.
RX PubMed=12106943; DOI=10.1016/s0735-1097(02)01962-9;
RA Smits J.P.P., Eckardt L., Probst V., Bezzina C.R., Schott J.-J.,
RA Remme C.A., Haverkamp W., Breithardt G., Escande D., Schulze-Bahr E.,
RA LeMarec H., Wilde A.A.M.;
RT "Genotype-phenotype relationship in Brugada syndrome: electrocardiographic
RT features differentiate SCN5A-related patients from non-SCN5A-related
RT patients.";
RL J. Am. Coll. Cardiol. 40:350-356(2002).
RN [53]
RP CHARACTERIZATION OF VARIANTS PFHB1A SER-298 AND ASN-1595.
RX PubMed=11804990; DOI=10.1161/hc0302.102592;
RA Wang D.W., Viswanathan P.C., Balser J.R., George A.L. Jr., Benson D.W.;
RT "Clinical, genetic and biophysical characterisation of SCN5A mutations
RT associated with atrioventricular conduction block.";
RL Circulation 105:341-346(2002).
RN [54]
RP MODELING OF VARIANT LQT3/BRGDA1 ASP-1795 INS.
RX PubMed=11889015; DOI=10.1161/hc1002.105183;
RA Clancy C.E., Rudy Y.;
RT "Na(+) channel mutation that causes both Brugada and long-QT syndrome
RT phenotypes: a simulation study of mechanism.";
RL Circulation 105:1208-1213(2002).
RN [55]
RP VARIANTS BRGDA1 HIS-27; VAL-226; VAL-230; HIS-282; MET-294; SER-319;
RP PHE-393 DEL; GLN-567; PRO-681; GLU-735; LEU-851; ILE-892; SER-896; LEU-910;
RP CYS-965; LYS-1053; ASN-1236; SER-1293; LYS-1500 DEL; ARG-1740; LYS-1784;
RP HIS-1795 AND LEU-1951, AND VARIANT GLN-1240.
RX PubMed=11901046; DOI=10.1161/hc1102.105288;
RA Priori S.G., Napolitano C., Gasparini M., Pappone C., Della Bella P.,
RA Giordano U., Bloise R., Giustetto C., De Nardis R., Grillo M.,
RA Ronchetti E., Faggiano G., Nastoli J.;
RT "Natural history of Brugada syndrome: insights for risk stratification and
RT management.";
RL Circulation 105:1342-1347(2002).
RN [56]
RP VARIANTS LQT3 GLU-615; PHE-619 AND LEU-1250, AND VARIANTS CYS-34 AND
RP ARG-558.
RX PubMed=11997281; DOI=10.1161/01.cir.0000014448.19052.4c;
RA Yang P., Kanki H., Drolet B., Yang T., Wei J., Viswanathan P.C.,
RA Hohnloser S.H., Shimizu W., Schwartz P.J., Stanton M., Murray K.T.,
RA Norris K., George A.L. Jr., Roden D.M.;
RT "Allelic variants in long-QT disease genes in patients with drug-associated
RT torsades de pointes.";
RL Circulation 105:1943-1948(2002).
RN [57]
RP CHARACTERIZATION OF VARIANTS BRGDA1 HIS-367; VAL-735 AND GLN-1193.
RX PubMed=11823453; DOI=10.1093/hmg/11.3.337;
RA Vatta M., Dumaine R., Varghese G., Richard T.A., Shimizu W., Aihara N.,
RA Nademanee K., Brugada R., Brugada J., Veerakul G., Li H., Bowles N.E.,
RA Brugada P., Antzelevitch C., Towbin J.A.;
RT "Genetic and biophysical basis of sudden unexplained nocturnal death
RT syndrome (SUNDS), a disease allelic to Brugada syndrome.";
RL Hum. Mol. Genet. 11:337-345(2002).
RN [58]
RP VARIANT TYR-1103.
RX PubMed=12471205; DOI=10.1136/jmg.39.12.913;
RA Chen S., Chung M.K., Martin D., Rozich R., Tchou P.J., Wang Q.;
RT "SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with
RT cardiac arrhythmias and sudden death in a white family.";
RL J. Med. Genet. 39:913-915(2002).
RN [59]
RP VARIANTS BRGDA1 GLU-126 AND VAL-351, CHARACTERIZATION OF VARIANT BRGDA1
RP VAL-351, AND VARIANT ARG-558.
RX PubMed=12051963; DOI=10.1016/s1096-7192(02)00006-9;
RA Vatta M., Dumaine R., Antzelevitch C., Brugada R., Li H., Bowles N.E.,
RA Nademanee K., Brugada J., Brugada P., Towbin J.A.;
RT "Novel mutations in domain I of SCN5A cause Brugada syndrome.";
RL Mol. Genet. Metab. 75:317-324(2002).
RN [60]
RP VARIANT LQT3 VAL-1768, AND CHARACTERIZATION OF VARIANT LQT3 VAL-1768.
RX PubMed=12209021; DOI=10.1152/physiolgenomics.00039.2002;
RA Rivolta I., Clancy C.E., Tateyama M., Liu H., Priori S.G., Kass R.S.;
RT "A novel SCN5A mutation associated with long QT-3: altered inactivation
RT kinetics and channel dysfunction.";
RL Physiol. Genomics 10:191-197(2002).
RN [61]
RP VARIANT TYR-1103.
RX PubMed=12193783; DOI=10.1126/science.1073569;
RA Splawski I., Timothy K.W., Tateyama M., Clancy C.E., Malhotra A.,
RA Beggs A.H., Cappuccio F.P., Sagnella G.A., Kass R.S., Keating M.T.;
RT "Variant of SCN5A sodium channel implicated in risk of cardiac
RT arrhythmia.";
RL Science 297:1333-1336(2002).
RN [62]
RP VARIANT ATRST1 ASN-1275.
RX PubMed=12522116; DOI=10.1161/01.res.0000050585.07097.d7;
RA Groenewegen W.A., Firouzi M., Bezzina C.R., Vliex S., van Langen I.M.,
RA Sandkuijl L., Smits J.P., Hulsbeek M., Rook M.B., Jongsma H.J.,
RA Wilde A.A.M.;
RT "A cardiac sodium channel mutation cosegregates with a rare connexin40
RT genotype in familial atrial standstill.";
RL Circ. Res. 92:14-22(2003).
RN [63]
RP VARIANT PFHB1A TRP-225.
RX PubMed=12574143; DOI=10.1161/01.res.0000052672.97759.36;
RA Bezzina C.R., Rook M.B., Groenewegen W.A., Herfst L.J., van der Wal A.C.,
RA Lam J., Jongsma H.J., Wilde A.A.M., Mannens M.M.;
RT "Compound heterozygosity for mutations (W156X and R225W) in SCN5A
RT associated with severe cardiac conduction disturbances and degenerative
RT changes in the conduction system.";
RL Circ. Res. 92:159-168(2003).
RN [64]
RP VARIANT LQT3 PHE-619.
RX PubMed=12673799; DOI=10.1002/humu.9136;
RA Wehrens X.H., Rossenbacker T., Jongbloed R.J., Gewillig M., Heidbuchel H.,
RA Doevendans P.A., Vos M.A., Wellens H.J., Kass R.S.;
RT "A novel mutation L619F in the cardiac Na+ channel SCN5A associated with
RT long-QT syndrome (LQT3): a role for the I-II linker in inactivation
RT gating.";
RL Hum. Mutat. 21:552-552(2003).
RN [65]
RP VARIANT PFHB1A ILE-512, CHARACTERIZATION OF VARIANT PFHB1A ILE-512, VARIANT
RP ARG-558, AND CHARACTERIZATION OF VARIANT ARG-558.
RX PubMed=12569159; DOI=10.1172/jci200316879;
RA Viswanathan P.C., Benson D.W., Balser J.R.;
RT "A common SCN5A polymorphism modulates the biophysical effects of an SCN5A
RT mutation.";
RL J. Clin. Invest. 111:341-346(2003).
RN [66]
RP VARIANTS SSS1 ILE-220; LEU-1298 AND ARG-1408.
RX PubMed=14523039; DOI=10.1172/jci200318062;
RA Benson D.W., Wang D.W., Dyment M., Knilans T.K., Fish F.A., Strieper M.J.,
RA Rhodes T.H., George A.L. Jr.;
RT "Congenital sick sinus syndrome caused by recessive mutations in the
RT cardiac sodium channel gene (SCN5A).";
RL J. Clin. Invest. 112:1019-1028(2003).
RN [67]
RP VARIANT BRGDA1 ARG-1743, AND CHARACTERIZATION OF VARIANT BRGDA1 ARG-1743.
RX PubMed=15023552; DOI=10.1016/j.cardiores.2004.01.022;
RA Valdivia C.R., Tester D.J., Rok B.A., Porter C.B., Munger T.M.,
RA Jahangir A., Makielski J.C., Ackerman M.J.;
RT "A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued
RT by drugs.";
RL Cardiovasc. Res. 62:53-62(2004).
RN [68]
RP VARIANT CMD1E ASN-1275.
RX PubMed=15466643; DOI=10.1161/01.cir.0000144458.58660.bb;
RG The familial cardiomyopathy registry research group;
RA McNair W.P., Ku L., Taylor M.R.G., Fain P.R., Dao D., Wolfel E.,
RA Mestroni L.;
RT "SCN5A mutation associated with dilated cardiomyopathy, conduction
RT disorder, and arrhythmia.";
RL Circulation 110:2163-2167(2004).
RN [69]
RP VARIANT BRGDA1 SER-1262.
RX PubMed=15338453; DOI=10.1007/s10038-004-0182-z;
RA Shin D.-J., Jang Y., Park H.-Y., Lee J.E., Yang K., Kim E., Bae Y., Kim J.,
RA Kim J., Kim S.S., Lee M.H., Chahine M., Yoon S.K.;
RT "Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with
RT Brugada syndrome.";
RL J. Hum. Genet. 49:573-578(2004).
RN [70]
RP VARIANT BRGDA1 LYS-1053, CHARACTERIZATION OF VARIANT BRGDA1 LYS-1053, AND
RP INTERACTION WITH ANK3.
RX PubMed=15579534; DOI=10.1073/pnas.0403711101;
RA Mohler P.J., Rivolta I., Napolitano C., LeMaillet G., Lambert S.,
RA Priori S.G., Bennett V.;
RT "Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-
RT G and expression of Nav1.5 on the surface of cardiomyocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17533-17538(2004).
RN [71]
RP VARIANT BRGDA1 GLY-1714, AND CHARACTERIZATION OF VARIANT BRGDA1 GLY-1714.
RX PubMed=16266370; DOI=10.1111/j.1365-201x.2005.01496.x;
RA Amin A.S., Verkerk A.O., Bhuiyan Z.A., Wilde A.A.M., Tan H.L.;
RT "Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac
RT Na+ channel does not affect ion selectivity properties.";
RL Acta Physiol. Scand. 185:291-301(2005).
RN [72]
RP VARIANTS BRGDA1 ARG-1527 AND PRO-1569.
RX PubMed=15851320; DOI=10.1016/j.hrthm.2004.11.022;
RA Yokoi H., Makita N., Sasaki K., Takagi Y., Okumura Y., Nishino T.,
RA Makiyama T., Kitabatake A., Horie M., Watanabe I., Tsutsui H.;
RT "Double SCN5A mutation underlying asymptomatic Brugada syndrome.";
RL Heart Rhythm 2:285-292(2005).
RN [73]
RP VARIANTS LQT3 GLU-413; THR-413; GLU-573; ARG-579; HIS-689; PRO-1626;
RP CYS-1644; VAL-1660; CYS-1767; GLY-1790 AND HIS-1913, AND VARIANTS THR-1498
RP AND ASN-1787.
RX PubMed=16414944; DOI=10.1001/jama.294.23.2975;
RA Napolitano C., Priori S.G., Schwartz P.J., Bloise R., Ronchetti E.,
RA Nastoli J., Bottelli G., Cerrone M., Leonardi S.;
RT "Genetic testing in the long QT syndrome: development and validation of an
RT efficient approach to genotyping in clinical practice.";
RL JAMA 294:2975-2980(2005).
RN [74]
RP VARIANTS LQT3 LEU-125; LYS-245; GLN-404; LYS-406; MET-411; LYS-462;
RP ASP-572; GLU-615; LEU-637; LEU-648; CYS-971; MET-1069; LYS-1225; LYS-1231;
RP SER-1325; TYR-1458; GLU-1481; 1505-LYS--GLN-1507 DEL; LEU-1623; HIS-1644;
RP ILE-1667; MET-1763; LEU-1766; MET-1777; MET-1779; LYS-1784; CYS-1795;
RP ARG-1909 AND SER-1949, AND VARIANTS TRP-18; PHE-618 AND GLN-1958.
RX PubMed=15840476; DOI=10.1016/j.hrthm.2005.01.020;
RA Tester D.J., Will M.L., Haglund C.M., Ackerman M.J.;
RT "Compendium of cardiac channel mutations in 541 consecutive unrelated
RT patients referred for long QT syndrome genetic testing.";
RL Heart Rhythm 2:507-517(2005).
RN [75]
RP VARIANTS BRGDA1 ILE-187 AND ASN-356, AND CHARACTERIZATION OF VARIANTS
RP BRGDA1 ILE-187 AND ASN-356.
RX PubMed=16325048; DOI=10.1016/j.jacc.2005.08.043;
RA Makiyama T., Akao M., Tsuji K., Doi T., Ohno S., Takenaka K., Kobori A.,
RA Ninomiya T., Yoshida H., Takano M., Makita N., Yanagisawa F., Higashi Y.,
RA Takeyama Y., Kita T., Horie M.;
RT "High risk for bradyarrhythmic complications in patients with Brugada
RT syndrome caused by SCN5A gene mutations.";
RL J. Am. Coll. Cardiol. 46:2100-2106(2005).
RN [76]
RP VARIANT BRGDA1 SER-1344, AND VARIANTS ARG-552 AND GLN-1027.
RX PubMed=16616735; DOI=10.1016/j.cardiores.2006.02.030;
RA Keller D.I., Huang H., Zhao J., Frank R., Suarez V., Delacretaz E.,
RA Brink M., Osswald S., Schwick N., Chahine M.;
RT "A novel SCN5A mutation, F1344S, identified in a patient with Brugada
RT syndrome and fever-induced ventricular fibrillation.";
RL Cardiovasc. Res. 70:521-529(2006).
RN [77]
RP VARIANTS BRGDA1 LEU-336 AND VAL-1660, AND CHARACTERIZATION OF VARIANTS
RP BRGDA1 LEU-336 AND VAL-1660.
RX PubMed=17075016; DOI=10.1161/circulationaha.106.627489;
RA Cordeiro J.M., Barajas-Martinez H., Hong K., Burashnikov E., Pfeiffer R.,
RA Orsino A.M., Wu Y.S., Hu D., Brugada J., Brugada P., Antzelevitch C.,
RA Dumaine R., Brugada R.;
RT "Compound heterozygous mutations P336L and I1660V in the human cardiac
RT sodium channel associated with the Brugada syndrome.";
RL Circulation 114:2026-2033(2006).
RN [78]
RP VARIANTS LQT3 VAL-9; GLN-225; ARG-639; TYR-1333; TRP-1609 AND ASN-1819.
RX PubMed=16922724; DOI=10.1111/j.1399-0004.2006.00671.x;
RA Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P.,
RA Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V.,
RA Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.;
RT "Spectrum of pathogenic mutations and associated polymorphisms in a cohort
RT of 44 unrelated patients with long QT syndrome.";
RL Clin. Genet. 70:214-227(2006).
RN [79]
RP VARIANTS BRGDA1 ILE-95; PHE-1617 DEL AND VAL-1649.
RX PubMed=17081365;
RA Liang P., Liu W.L., Hu D.Y., Li C.L., Tao W.H., Li L.;
RT "Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V
RT and delF1617.";
RL Zhonghua Xin Xue Guan Bing Za Zhi 34:616-619(2006).
RN [80]
RP VARIANT LQT3 LEU-1904, AND CHARACTERIZATION OF VARIANT LQT3 LEU-1904.
RX PubMed=18708744; DOI=10.4161/chan.4956;
RA Bankston J.R., Sampson K.J., Kateriya S., Glaaser I.W., Malito D.L.,
RA Chung W.K., Kass R.S.;
RT "A novel LQT-3 mutation disrupts an inactivation gate complex with distinct
RT rate-dependent phenotypic consequences.";
RL Channels 1:273-280(2007).
RN [81]
RP VARIANT BRGDA1 ILE-353.
RX PubMed=17198989; DOI=10.1016/j.hrthm.2006.09.031;
RA Pfahnl A.E., Viswanathan P.C., Weiss R., Shang L.L., Sanyal S.,
RA Shusterman V., Kornblit C., London B., Dudley S.C. Jr.;
RT "A sodium channel pore mutation causing Brugada syndrome.";
RL Heart Rhythm 4:46-53(2007).
RN [82]
RP VARIANT LQT3 CYS-1473.
RX PubMed=18060054; DOI=10.1371/journal.pone.0001258;
RA Bankston J.R., Yue M., Chung W., Spyres M., Pass R.H., Silver E.,
RA Sampson K.J., Kass R.S.;
RT "A novel and lethal de novo LQT-3 mutation in a newborn with distinct
RT molecular pharmacology and therapeutic response.";
RL PLoS ONE 2:E1258-E1258(2007).
RN [83]
RP VARIANT BRGDA1 ASN-1494.
RX PubMed=18341814;
RA Tian L., Zhu J.F., Yang J.G.;
RT "Gene (SCN5A) mutation analysis of a Chinese family with Brugada
RT syndrome.";
RL Zhonghua Xin Xue Guan Bing Za Zhi 35:1122-1125(2007).
RN [84]
RP VARIANT BRGDA1 CYS-878.
RX PubMed=18616619; DOI=10.1111/j.1748-1716.2008.01883.x;
RA Zhang Y., Wang T., Ma A., Zhou X., Gui J., Wan H., Shi R., Huang C.,
RA Grace A.A., Huang C.L., Trump D., Zhang H., Zimmer T., Lei M.;
RT "Correlations between clinical and physiological consequences of the novel
RT mutation R878C in a highly conserved pore residue in the cardiac Na+
RT channel.";
RL Acta Physiol. 194:311-323(2008).
RN [85]
RP VARIANT BRGDA1 LEU-2004, AND CHARACTERIZATION OF VARIANT BRGDA1 LEU-2004.
RX PubMed=18456723; DOI=10.1152/ajpheart.91495.2007;
RA Bebarova M., O'Hara T., Geelen J.L.M.C., Jongbloed R.J., Timmermans C.,
RA Arens Y.H., Rodriguez L.-M., Rudy Y., Volders P.G.A.;
RT "Subepicardial phase 0 block and discontinuous transmural conduction
RT underlie right precordial ST-segment elevation by a SCN5A loss-of-function
RT mutation.";
RL Am. J. Physiol. 295:H48-H58(2008).
RN [86]
RP VARIANT BRGDA1 SER-1850, AND CHARACTERIZATION OF VARIANT BRGDA1 SER-1850.
RX PubMed=18252757; DOI=10.1093/cvr/cvn023;
RA Petitprez S., Jespersen T., Pruvot E., Keller D.I., Corbaz C.,
RA Schlapfer J., Abriel H., Kucera J.P.;
RT "Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization
RT disorder hypotheses in the Brugada syndrome.";
RL Cardiovasc. Res. 78:494-504(2008).
RN [87]
RP VARIANTS ILE-232 AND PHE-1308.
RX PubMed=18599870; DOI=10.1161/circresaha.108.172619;
RA Barajas-Martinez H.M., Hu D., Cordeiro J.M., Wu Y., Kovacs R.J.,
RA Meltser H., Kui H., Elena B., Brugada R., Antzelevitch C., Dumaine R.;
RT "Lidocaine-induced Brugada syndrome phenotype linked to a novel double
RT mutation in the cardiac sodium channel.";
RL Circ. Res. 103:396-404(2008).
RN [88]
RP VARIANTS ATFB10 ILE-138; LYS-428; ASP-445; LYS-470; ASP-572; LYS-655;
RP LYS-1053; ILE-1131; CYS-1826 AND MET-1951, AND VARIANTS CYS-34; LEU-216;
RP HIS-376; VAL-461; TRP-481; TYR-524; ARG-558; PHE-618; SER-997; TYR-1103;
RP GLN-1193; LEU-1951 AND LEU-2004.
RX PubMed=18378609; DOI=10.1161/circulationaha.107.757955;
RA Darbar D., Kannankeril P.J., Donahue B.S., Kucera G., Stubblefield T.,
RA Haines J.L., George A.L. Jr., Roden D.M.;
RT "Cardiac sodium channel (SCN5A) variants associated with atrial
RT fibrillation.";
RL Circulation 117:1927-1935(2008).
RN [89]
RP VARIANT ATFB10 LYS-1987.
RX PubMed=18088563; DOI=10.1016/j.hrthm.2007.09.015;
RA Ellinor P.T., Nam E.G., Shea M.A., Milan D.J., Ruskin J.N., MacRae C.A.;
RT "Cardiac sodium channel mutation in atrial fibrillation.";
RL Heart Rhythm 5:99-105(2008).
RN [90]
RP VARIANT LQT3 CYS-1795.
RX PubMed=18929331; DOI=10.1016/j.hrthm.2008.07.013;
RA Benito B., Brugada R., Perich R.M., Lizotte E., Cinca J., Mont L.,
RA Berruezo A., Tolosana J.M., Freixa X., Brugada P., Brugada J.;
RT "A mutation in the sodium channel is responsible for the association of
RT long QT syndrome and familial atrial fibrillation.";
RL Heart Rhythm 5:1434-1440(2008).
RN [91]
RP VARIANT LQT3 GLN-43, AND CHARACTERIZATION OF VARIANT LQT3 GLN-43.
RX PubMed=18848812; DOI=10.1016/j.hrthm.2008.08.010;
RA Lin M.-T., Wu M.-H., Chang C.-C., Chiu S.-N., Theriault O., Huang H.,
RA Christe G., Ficker E., Chahine M.;
RT "In utero onset of long QT syndrome with atrioventricular block and
RT spontaneous or lidocaine-induced ventricular tachycardia: compound effects
RT of hERG pore region mutation and SCN5A N-terminus variant.";
RL Heart Rhythm 5:1567-1574(2008).
RN [92]
RP VARIANT ATRIAL FIBRILLATION THR-1875, AND CHARACTERIZATION OF VARIANT
RP ATRIAL FIBRILLATION THR-1875.
RX PubMed=18929244; DOI=10.1016/j.jacc.2008.07.013;
RA Makiyama T., Akao M., Shizuta S., Doi T., Nishiyama K., Oka Y., Ohno S.,
RA Nishio Y., Tsuji K., Itoh H., Kimura T., Kita T., Horie M.;
RT "A novel SCN5A gain-of-function mutation M1875T associated with familial
RT atrial fibrillation.";
RL J. Am. Coll. Cardiol. 52:1326-1334(2008).
RN [93]
RP VARIANT LQT3/BRGDA1/SSS1 LYS-1784.
RX PubMed=18451998; DOI=10.1172/jci34057;
RA Makita N., Behr E., Shimizu W., Horie M., Sunami A., Crotti L.,
RA Schulze-Bahr E., Fukuhara S., Mochizuki N., Makiyama T., Itoh H.,
RA Christiansen M., McKeown P., Miyamoto K., Kamakura S., Tsutsui H.,
RA Schwartz P.J., George A.L. Jr., Roden D.M.;
RT "The E1784K mutation in SCN5A is associated with mixed clinical phenotype
RT of type 3 long QT syndrome.";
RL J. Clin. Invest. 118:2219-2229(2008).
RN [94]
RP VARIANTS ARG-558 AND LEU-1090.
RX PubMed=18368697; DOI=10.1016/j.ymgme.2007.10.009;
RA Shan L., Makita N., Xing Y., Watanabe S., Futatani T., Ye F., Saito K.,
RA Ibuki K., Watanabe K., Hirono K., Uese K., Ichida F., Miyawaki T.,
RA Origasa H., Bowles N.E., Towbin J.A.;
RT "SCN5A variants in Japanese patients with left ventricular noncompaction
RT and arrhythmia.";
RL Mol. Genet. Metab. 93:468-474(2008).
RN [95]
RP VARIANTS SIDS CYS-532; SER-1084 AND SER-1705, AND CHARACTERIZATION OF
RP VARIANT SIDS SER-1705.
RX PubMed=18596570; DOI=10.1203/pdr.0b013e3181841eca;
RA Otagiri T., Kijima K., Osawa M., Ishii K., Makita N., Matoba R., Umetsu K.,
RA Hayasaka K.;
RT "Cardiac ion channel gene mutations in sudden infant death syndrome.";
RL Pediatr. Res. 64:482-487(2008).
RN [96]
RP VARIANT IRRITABLE BOWEL SYNDROME SER-298, AND CHARACTERIZATION OF VARIANT
RP IRRITABLE BOWEL SYNDROME SER-298.
RX PubMed=19056759; DOI=10.1152/ajpgi.90571.2008;
RA Saito Y.A., Strege P.R., Tester D.J., Locke G.R. III, Talley N.J.,
RA Bernard C.E., Rae J.L., Makielski J.C., Ackerman M.J., Farrugia G.;
RT "Sodium channel mutation in irritable bowel syndrome: evidence for an ion
RT channelopathy.";
RL Am. J. Physiol. 296:G211-G218(2009).
RN [97]
RP VARIANT SIDS TYR-1333.
RX PubMed=19302788; DOI=10.1016/j.febslet.2009.02.007;
RA Huang H., Millat G., Rodriguez-Lafrasse C., Rousson R., Kugener B.,
RA Chevalier P., Chahine M.;
RT "Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS
RT infant linked to long QT syndrome.";
RL FEBS Lett. 583:890-896(2009).
RN [98]
RP VARIANTS BRGDA1 LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232;
RP ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND
RP THR-1924, AND VARIANTS PFHB1A LYS-161; CYS-367; HIS-367; CYS-514; ARG-752;
RP TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740;
RP GLU-1743 AND THR-1924.
RX PubMed=19251209; DOI=10.1016/j.hrthm.2008.11.009;
RA Meregalli P.G., Tan H.L., Probst V., Koopmann T.T., Tanck M.W.,
RA Bhuiyan Z.A., Sacher F., Kyndt F., Schott J.-J., Albuisson J., Mabo P.,
RA Bezzina C.R., Le Marec H., Wilde A.A.M.;
RT "Type of SCN5A mutation determines clinical severity and degree of
RT conduction slowing in loss-of-function sodium channelopathies.";
RL Heart Rhythm 6:341-348(2009).
RN [99]
RP VARIANTS LQT3 GLN-18; HIS-27; GLY-30; GLN-43; LYS-48; SER-52; GLN-53;
RP GLY-104; GLY-115; LEU-125; PRO-212; GLN-222; TRP-225; MET-240; LEU-247;
RP LYS-275; SER-289; TRP-340; CYS-367; MET-370; THR-397; LYS-406; VAL-409;
RP MET-411; GLU-429 DEL; ALA-462; VAL-530; GLN-535; TRP-569; ILE-571; SER-572;
RP VAL-572; 586-ALA-LEU-587 DEL; GLU-615; ARG-639; LYS-654; PRO-673; CYS-689;
RP LEU-701; ILE-731; ARG-750; ASN-772; TYR-816; PHE-848; LYS-960; LEU-965;
RP PHE-981; SER-997; ARG-1004; LYS-1053; MET-1069; VAL-1100; ASN-1114;
RP ASN-1166; SER-1199; ILE-1212 DEL; MET-1283; MET-1304; SER-1325; SER-1326;
RP VAL-1334; VAL-1338; SER-1432; SER-1472; CYS-1473; GLU-1481; LEU-1487;
RP ARG-1488; ASP-1489; ARG-1493; SER-1495; VAL-1498; VAL-1501; ASN-1505;
RP ILE-1532; PHE-1560; MET-1593; SER-1594; ILE-1596; PHE-1617 DEL; GLN-1623;
RP LEU-1623; HIS-1626; CYS-1644; PHE-1650; THR-1652; ASN-1723; TRP-1739;
RP HIS-1761; PHE-1761; MET-1763; MET-1777; MET-1779; LYS-1784; CYS-1795;
RP HIS-1826; GLY-1839; TRP-1897; GLN-1901; ASN-1977; VAL-2004 AND CYS-2012.
RX PubMed=19716085; DOI=10.1016/j.hrthm.2009.05.021;
RA Kapplinger J.D., Tester D.J., Salisbury B.A., Carr J.L., Harris-Kerr C.,
RA Pollevick G.D., Wilde A.A., Ackerman M.J.;
RT "Spectrum and prevalence of mutations from the first 2,500 consecutive
RT unrelated patients referred for the FAMILION long QT syndrome genetic
RT test.";
RL Heart Rhythm 6:1297-1303(2009).
RN [100]
RP VARIANT BRGDA1 CYS-965, AND CHARACTERIZATION OF VARIANT BRGDA1 CYS-965.
RX PubMed=19272188; DOI=10.1186/1423-0127-16-23;
RA Hsueh C.H., Chen W.P., Lin J.L., Tsai C.T., Liu Y.B., Juang J.M.,
RA Tsao H.M., Su M.J., Lai L.P.;
RT "Distinct functional defect of three novel Brugada syndrome related cardiac
RT sodium channel mutations.";
RL J. Biomed. Sci. 16:23-23(2009).
RN [101]
RP VARIANTS TRP-18; CYS-34; HIS-34; LEU-216; SER-286; SER-291; MET-299;
RP CYS-376; GLY-447; ALA-449; VAL-461; SER-475; TRP-481; TYR-524; ARG-558;
RP HIS-568; ARG-579; LYS-592; GLY-596; ALA-601; PHE-618; ASP-638; LEU-656;
RP THR-672; HIS-689; LYS-692; PHE-705; ILE-924; GLN-986; MET-1016; ARG-1040;
RP ALA-1082; LEU-1090; LEU-1098; TYR-1103; LYS-1107; TRP-1116; GLN-1193;
RP MET-1251; SER-1293; PHE-1308; TRP-1512; ASN-1787; THR-1836; LYS-1901;
RP CYS-1919; LEU-1951; GLN-1958; LEU-1962; MET-1968; GLN-1991; LEU-2004 AND
RP ALA-2006, AND VARIANTS BRGDA1 GLN-18; LYS-70; ASN-84; SER-93; SER-94;
RP GLN-104; TRP-104; LYS-109; GLN-121; TRP-121; GLU-126; PRO-136; MET-146;
RP GLN-161; LYS-161; ASN-175; GLY-178; ARG-182; VAL-185; VAL-204; GLN-212;
RP ILE-220; GLN-222; LEU-223; TRP-225; VAL-226; ILE-232; MET-240; LYS-270;
RP GLN-276; ASP-278; CYS-282; ILE-300; PRO-315; ASN-320; ARG-325; LEU-336;
RP ASP-351; VAL-351; ASN-356; CYS-367; HIS-367; LEU-367; LYS-369; GLY-374;
RP HIS-376; ARG-386; GLU-386; ALA-396; LEU-396; LYS-439; GLY-501; HIS-526;
RP CYS-532; LEU-543; ARG-552; GLU-615; PHE-619; CYS-620; MET-632; ALA-640;
RP ASP-647; LEU-648; TRP-661; GLY-683; LEU-701; LEU-717; VAL-735; LYS-746;
RP ARG-752; GLU-758; ARG-764; ASN-772; SER-773; ILE-789; PRO-808; PRO-839;
RP LEU-851; GLN-867; CYS-878; HIS-878; PRO-886; CYS-893; HIS-893; LYS-901;
RP LEU-910; ARG-915; ARG-917; SER-927; PRO-928; PRO-935; CYS-965; HIS-965;
RP THR-997; LYS-1053; GLY-1055; TYR-1079; VAL-1113; THR-1140; ASN-1219;
RP LYS-1225; HIS-1228; GLN-1232; TRP-1232; PRO-1239; ASN-1243; ASP-1249;
RP GLY-1253; SER-1262; CYS-1271; ASN-1275; GLY-1288; PRO-1311; VAL-1319;
RP GLY-1323; LEU-1332; LEU-1344; ILE-1346; PRO-1346; ARG-1351; MET-1353;
RP TRP-1358; ASN-1359; CYS-1360; TYR-1363; ILE-1382; LEU-1405; MET-1405;
RP ARG-1406; GLU-1406; ARG-1408; CYS-1409; PHE-1412; GLU-1419; ARG-1420;
RP SER-1427; VAL-1428; GLY-1432; SER-1432; VAL-1433; LEU-1438; GLN-1441;
RP LEU-1448; THR-1448; CYS-1449; ASP-1451; TYR-1463; PHE-1468; VAL-1501;
RP LYS-1521; MET-1525; LYS-1548; CYS-1571; LYS-1574; PRO-1582; CYS-1583;
RP HIS-1583; MET-1604; LEU-1613; MET-1620; GLN-1623; GLN-1629; GLU-1642;
RP VAL-1660; ARG-1661; ILE-1667; TYR-1672; THR-1680; THR-1698; ARG-1709;
RP MET-1709; SER-1712; GLY-1714; ASP-1722; ARG-1728; TRP-1728; ARG-1740;
RP ARG-1743; GLU-1743; PHE-1764; MET-1779; LYS-1784; GLU-1832; ILE-1861;
RP ASN-1872; LEU-1903; THR-1924; SER-1935; LYS-1938 AND VAL-2004.
RX PubMed=20129283; DOI=10.1016/j.hrthm.2009.09.069;
RA Kapplinger J.D., Tester D.J., Alders M., Benito B., Berthet M., Brugada J.,
RA Brugada P., Fressart V., Guerchicoff A., Harris-Kerr C., Kamakura S.,
RA Kyndt F., Koopmann T.T., Miyamoto Y., Pfeiffer R., Pollevick G.D.,
RA Probst V., Zumhagen S., Vatta M., Towbin J.A., Shimizu W., Schulze-Bahr E.,
RA Antzelevitch C., Salisbury B.A., Guicheney P., Wilde A.A., Brugada R.,
RA Schott J.J., Ackerman M.J.;
RT "An international compendium of mutations in the SCN5A-encoded cardiac
RT sodium channel in patients referred for Brugada syndrome genetic testing.";
RL Heart Rhythm 7:33-46(2010).
RN [102]
RP CHARACTERIZATION OF VARIANTS ARG-558 AND ALA-2006.
RX PubMed=21109022; DOI=10.1016/j.hrthm.2010.11.034;
RA Shinlapawittayatorn K., Du X.X., Liu H., Ficker E., Kaufman E.S.,
RA Deschenes I.;
RT "A common SCN5A polymorphism modulates the biophysical defects of SCN5A
RT mutations.";
RL Heart Rhythm 8:455-462(2011).
RN [103]
RP VARIANTS SSS1 VAL-735 AND ASN-1792.
RX PubMed=22795782; DOI=10.1016/j.arcped.2012.04.017;
RA Selly J.B., Boumahni B., Edmar A., Jamal Bey K., Randrianaivo H.,
RA Clerici G., Millat G., Caillet D.;
RT "Cardiac sinus node dysfunction due to a new mutation of the SCN5A gene.";
RL Arch. Pediatr. 19:837-841(2012).
RN [104]
RP VARIANT ARG-558, VARIANTS BRGDA1 ASN-1690 AND ASP-1748, CHARACTERIZATION OF
RP VARIANTS BRGDA1 ASN-1690 AND ASP-1748, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23085483; DOI=10.1016/j.hrthm.2012.10.025;
RA Nunez L., Barana A., Amoros I., de la Fuente M.G., Dolz-Gaiton P.,
RA Gomez R., Rodriguez-Garcia I., Mosquera I., Monserrat L., Delpon E.,
RA Caballero R., Castro-Beiras A., Tamargo J.;
RT "p.D1690N Nav1.5 rescues p.G1748D mutation gating defects in a compound
RT heterozygous Brugada syndrome patient.";
RL Heart Rhythm 10:264-272(2013).
RN [105]
RP VARIANT BRGDA1 GLN-1629, CHARACTERIZATION OF VARIANT BRGDA1 GLN-1629, AND
RP FUNCTION.
RX PubMed=24167619; DOI=10.1371/journal.pone.0078382;
RA Zeng Z., Zhou J., Hou Y., Liang X., Zhang Z., Xu X., Xie Q., Li W.,
RA Huang Z.;
RT "Electrophysiological characteristics of a SCN5A voltage sensors mutation
RT R1629Q associated with Brugada syndrome.";
RL PLoS ONE 8:E78382-E78382(2013).
RN [106]
RP VARIANT BRGDA1 GLN-812, CHARACTERIZATION OF VARIANT BRGDA1 GLN-812,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26279430; DOI=10.1159/000430189;
RA Wang L., Meng X., Yuchi Z., Zhao Z., Xu D., Fedida D., Wang Z., Huang C.;
RT "De novo mutation in the SCN5A gene associated with brugada syndrome.";
RL Cell. Physiol. Biochem. 36:2250-2262(2015).
RN [107]
RP VARIANT LQT3 ARG-1849, CHARACTERIZATION OF VARIANT LQT3 ARG-1849, FUNCTION,
RP AND INTERACTION WITH FGF12; FGF13 AND FGF14.
RX PubMed=26392562; DOI=10.1073/pnas.1516430112;
RA Musa H., Kline C.F., Sturm A.C., Murphy N., Adelman S., Wang C., Yan H.,
RA Johnson B.L., Csepe T.A., Kilic A., Higgins R.S., Janssen P.M.,
RA Fedorov V.V., Weiss R., Salazar C., Hund T.J., Pitt G.S., Mohler P.J.;
RT "SCN5A variant that blocks fibroblast growth factor homologous factor
RT regulation causes human arrhythmia.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:12528-12533(2015).
RN [108]
RP VARIANT BRGDA1 GLU-817, CHARACTERIZATION OF VARIANT BRGDA1 GLU-817, AND
RP FUNCTION.
RX PubMed=26776555; DOI=10.1016/j.hrthm.2016.01.008;
RA Kinoshita K., Takahashi H., Hata Y., Nishide K., Kato M., Fujita H.,
RA Yoshida S., Murai K., Mizumaki K., Nishida K., Yamaguchi Y., Kano M.,
RA Tabata T., Nishida N.;
RT "SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the
RT activation gating of NaV1.5 channel.";
RL Heart Rhythm 13:1113-1120(2016).
RN [109]
RP VARIANT BRGDA1 LEU-1571, AND CHARACTERIZATION OF VARIANT BRGDA1 LEU-1571.
RX PubMed=32850980; DOI=10.3389/fcvm.2020.00117;
RA Nijak A., Labro A.J., De Wilde H., Dewals W., Peigneur S., Tytgat J.,
RA Snyders D., Sieliwonczyk E., Simons E., Van Craenenbroeck E., Schepers D.,
RA Van Laer L., Saenen J., Loeys B., Alaerts M.;
RT "Compound heterozygous SCN5A mutations in severe sodium channelopathy with
RT Brugada syndrome: a case report.";
RL Front. Cardiovasc. Med. 7:117-117(2020).
CC -!- FUNCTION: This protein mediates the voltage-dependent sodium ion
CC permeability of excitable membranes. Assuming opened or closed
CC conformations in response to the voltage difference across the
CC membrane, the protein forms a sodium-selective channel through which
CC Na(+) ions may pass in accordance with their electrochemical gradient
CC (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830,
CC PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It
CC is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946).
CC This channel is responsible for the initial upstroke of the action
CC potential. Channel inactivation is regulated by intracellular calcium
CC levels (PubMed:19074138). {ECO:0000269|PubMed:1309946,
CC ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824,
CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830,
CC ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050,
CC ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562,
CC ECO:0000269|PubMed:26776555}.
CC -!- SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1
CC and SNTB2 (By similarity). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L
CC (PubMed:15217910, PubMed:15548568, PubMed:19666841). Interacts with
CC CALM (PubMed:21167176, PubMed:22705208, PubMed:25370050). Interacts
CC with FGF13; the interaction is direct and FGF13 may regulate SNC5A
CC density at membranes and function (PubMed:21817159, PubMed:22705208,
CC PubMed:26392562). May also interact with FGF12 and FGF14
CC (PubMed:26392562). Interacts with the spider Jingzhaotoxin-I (AC
CC P83974, AC B1P1B7, AC B1P1B8) (PubMed:26721415). Interacts with ANK3
CC (PubMed:15579534). {ECO:0000250|UniProtKB:Q9JJV9,
CC ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568,
CC ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:19666841,
CC ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:21817159,
CC ECO:0000269|PubMed:22705208, ECO:0000269|PubMed:25370050,
CC ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26721415}.
CC -!- INTERACTION:
CC Q14524; P62158: CALM3; NbExp=14; IntAct=EBI-726858, EBI-397435;
CC Q14524; Q13557: CAMK2D; NbExp=16; IntAct=EBI-726858, EBI-351018;
CC Q14524; P61328-2: FGF12; NbExp=4; IntAct=EBI-726858, EBI-10699759;
CC Q14524; P26045: PTPN3; NbExp=2; IntAct=EBI-726858, EBI-1047946;
CC Q14524-3; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-14276801, EBI-11954519;
CC Q14524-3; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-14276801, EBI-11524452;
CC Q14524-3; Q9Y3B6: EMC9; NbExp=3; IntAct=EBI-14276801, EBI-748366;
CC Q14524-3; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-14276801, EBI-750487;
CC Q14524-3; Q96E35: ZMYND19; NbExp=4; IntAct=EBI-14276801, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1309946,
CC ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824,
CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830,
CC ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cytoplasm, perinuclear
CC region {ECO:0000269|PubMed:21447824}. Cell membrane, sarcolemma, T-
CC tubule {ECO:0000250|UniProtKB:P15389}. Note=RANGRF promotes trafficking
CC to the cell membrane. {ECO:0000269|PubMed:21447824,
CC ECO:0000269|PubMed:23420830}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=CAG-inclusive variant, Nav1.5c;
CC IsoId=Q14524-1; Sequence=Displayed;
CC Name=2; Synonyms=Nav1.5b;
CC IsoId=Q14524-2; Sequence=VSP_037478;
CC Name=3;
CC IsoId=Q14524-3; Sequence=VSP_037477, VSP_037478, VSP_037481;
CC Name=4; Synonyms=Nav1.5e, neonatal;
CC IsoId=Q14524-4; Sequence=VSP_037477;
CC Name=5; Synonyms=Ex18del, Nav1.5a;
CC IsoId=Q14524-5; Sequence=VSP_037477, VSP_037479;
CC Name=6; Synonyms=Ex24del, Nav1.5f;
CC IsoId=Q14524-6; Sequence=VSP_037477, VSP_037480;
CC -!- TISSUE SPECIFICITY: Found in jejunal circular smooth muscle cells (at
CC protein level). Expressed in human atrial and ventricular cardiac
CC muscle but not in adult skeletal muscle, brain, myometrium, liver, or
CC spleen. Isoform 4 is expressed in brain. {ECO:0000269|PubMed:12358675}.
CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged
CC segment (S4). Segments S4 are probably the voltage-sensors and are
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000305}.
CC -!- DOMAIN: The IQ domain mediates association with calmodulin.
CC {ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:22705208}.
CC -!- PTM: Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not
CC seem to be ubiquitinated by NEDD4 or WWP2.
CC {ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568}.
CC -!- PTM: Phosphorylation at Ser-1503 by PKC in a highly conserved
CC cytoplasmic loop slows inactivation of the sodium channel and reduces
CC peak sodium currents (Probable). Regulated through phosphorylation by
CC CaMK2D (By similarity). {ECO:0000250|UniProtKB:Q9JJV9,
CC ECO:0000305|PubMed:19666841}.
CC -!- PTM: Lacks the cysteine which covalently binds the conotoxin GVIIJ.
CC This cysteine (position 868) is speculated in other sodium channel
CC subunits alpha to be implied in covalent binding with the sodium
CC channel subunit beta-2 or beta-4. {ECO:0000250|UniProtKB:P15389}.
CC -!- DISEASE: Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A
CC cardiac bundle branch disorder characterized by progressive alteration
CC of cardiac conduction through the His-Purkinje system, with a pattern
CC of a right bundle-branch block and/or left anterior hemiblock occurring
CC individually or together. It leads to complete atrio-ventricular block
CC causing syncope and sudden death. {ECO:0000269|PubMed:11234013,
CC ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159,
CC ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209,
CC ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Long QT syndrome 3 (LQT3) [MIM:603830]: A heart disorder
CC characterized by a prolonged QT interval on the ECG and polymorphic
CC ventricular arrhythmias. They cause syncope and sudden death in
CC response to exercise or emotional stress, and can present with a
CC sentinel event of sudden cardiac death in infancy.
CC {ECO:0000269|PubMed:10377081, ECO:0000269|PubMed:10508990,
CC ECO:0000269|PubMed:10590249, ECO:0000269|PubMed:10627139,
CC ECO:0000269|PubMed:10911008, ECO:0000269|PubMed:10973849,
CC ECO:0000269|PubMed:11304498, ECO:0000269|PubMed:11410597,
CC ECO:0000269|PubMed:11710892, ECO:0000269|PubMed:11889015,
CC ECO:0000269|PubMed:11997281, ECO:0000269|PubMed:12209021,
CC ECO:0000269|PubMed:12454206, ECO:0000269|PubMed:12673799,
CC ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944,
CC ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18060054,
CC ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18708744,
CC ECO:0000269|PubMed:18848812, ECO:0000269|PubMed:18929331,
CC ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:26392562,
CC ECO:0000269|PubMed:7651517, ECO:0000269|PubMed:7889574,
CC ECO:0000269|PubMed:8541846, ECO:0000269|PubMed:9506831,
CC ECO:0000269|PubMed:9686753, ECO:0000269|Ref.35}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Brugada syndrome 1 (BRGDA1) [MIM:601144]: A tachyarrhythmia
CC characterized by right bundle branch block and ST segment elevation on
CC an electrocardiogram (ECG). It can cause the ventricles to beat so fast
CC that the blood is prevented from circulating efficiently in the body.
CC When this situation occurs, the individual will faint and may die in a
CC few minutes if the heart is not reset. {ECO:0000269|PubMed:10532948,
CC ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:10690282,
CC ECO:0000269|PubMed:11410597, ECO:0000269|PubMed:11748104,
CC ECO:0000269|PubMed:11823453, ECO:0000269|PubMed:11901046,
CC ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12106943,
CC ECO:0000269|PubMed:15023552, ECO:0000269|PubMed:15338453,
CC ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:15851320,
CC ECO:0000269|PubMed:16266370, ECO:0000269|PubMed:16325048,
CC ECO:0000269|PubMed:16616735, ECO:0000269|PubMed:17075016,
CC ECO:0000269|PubMed:17081365, ECO:0000269|PubMed:17198989,
CC ECO:0000269|PubMed:18252757, ECO:0000269|PubMed:18341814,
CC ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18456723,
CC ECO:0000269|PubMed:18616619, ECO:0000269|PubMed:19251209,
CC ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:20129283,
CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830,
CC ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:26279430,
CC ECO:0000269|PubMed:26776555, ECO:0000269|PubMed:32850980,
CC ECO:0000269|PubMed:9521325}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Sick sinus syndrome 1 (SSS1) [MIM:608567]: The term 'sick
CC sinus syndrome' encompasses a variety of conditions caused by sinus
CC node dysfunction. The most common clinical manifestations are syncope,
CC presyncope, dizziness, and fatigue. Electrocardiogram typically shows
CC sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of
CC atrial tachycardias coexisting with sinus bradycardia ('tachycardia-
CC bradycardia syndrome') are also common in this disorder. SSS occurs
CC most often in the elderly associated with underlying heart disease or
CC previous cardiac surgery, but can also occur in the fetus, infant, or
CC child without heart disease or other contributing factors. SSS1 onset
CC is in utero, infancy, or early childhood. {ECO:0000269|PubMed:11748104,
CC ECO:0000269|PubMed:14523039, ECO:0000269|PubMed:22795782}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Familial paroxysmal ventricular fibrillation 1 (VF1)
CC [MIM:603829]: A cardiac arrhythmia marked by fibrillary contractions of
CC the ventricular muscle due to rapid repetitive excitation of myocardial
CC fibers without coordinated contraction of the ventricle and by absence
CC of atrial activity. {ECO:0000269|PubMed:10940383}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the
CC sudden death of an infant younger than 1 year that remains unexplained
CC after a thorough case investigation, including performance of a
CC complete autopsy, examination of the death scene, and review of
CC clinical history. Pathophysiologic mechanisms for SIDS may include
CC respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory
CC instability, and inborn errors of metabolism, but definitive pathogenic
CC mechanisms precipitating an infant sudden death remain elusive.
CC {ECO:0000269|PubMed:18596570, ECO:0000269|PubMed:19302788}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Atrial standstill 1 (ATRST1) [MIM:108770]: A rare arrhythmia
CC characterized by the absence of electrical and mechanical activity in
CC the atria. Electrocardiographically, it is characterized by
CC bradycardia, the absence of P waves, and a junctional narrow complex
CC escape rhythm. {ECO:0000269|PubMed:12522116,
CC ECO:0000269|PubMed:23420830}. Note=The disease may be caused by
CC variants affecting distinct genetic loci, including the gene
CC represented in this entry. A mutation in SCN5A has been detected in
CC combination with a rare GJA5 genotype in a large family with atrial
CC standstill.
CC -!- DISEASE: Cardiomyopathy, dilated 1E (CMD1E) [MIM:601154]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:15466643,
CC ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Atrial fibrillation, familial, 10 (ATFB10) [MIM:614022]: A
CC familial form of atrial fibrillation, a common sustained cardiac rhythm
CC disturbance. Atrial fibrillation is characterized by disorganized
CC atrial electrical activity and ineffective atrial contraction promoting
CC blood stasis in the atria and reduces ventricular filling. It can
CC result in palpitations, syncope, thromboembolic stroke, and congestive
CC heart failure. {ECO:0000269|PubMed:18088563,
CC ECO:0000269|PubMed:18378609}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Na(+) channels in mammalian cardiac membrane have
CC functional properties quite distinct from Na(+) channels in nerve and
CC skeletal muscle.
CC -!- MISCELLANEOUS: [Isoform 1]: Most abundant isoform in heart.
CC -!- MISCELLANEOUS: [Isoform 2]: Very abundant isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Abundantly expressed in neonatal brain and
CC heart, slower kinetics of activation and inactivation. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Only detected in neuroblastoma in humans.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: High expression in brain where it accounts
CC for nearly 50% of the total transcripts. Non-functional channel, may
CC exist to limit the number of undesired functional Nav1.5 channels.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.5/SCN5A subfamily. {ECO:0000305}.
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DR EMBL; M77235; AAA58644.1; -; mRNA.
DR EMBL; AY038064; AAK74065.1; -; mRNA.
DR EMBL; AY148488; AAN61120.1; -; mRNA.
DR EMBL; AF482988; AAO91669.1; -; mRNA.
DR EMBL; AB158469; BAD12084.1; -; mRNA.
DR EMBL; AB158470; BAD12085.1; -; mRNA.
DR EMBL; EF629346; ABR15763.1; -; mRNA.
DR EMBL; EF629347; ABR15764.1; -; mRNA.
DR EMBL; DQ784809; ABQ01244.1; -; Genomic_DNA.
DR EMBL; EF179185; ABN05288.1; -; Genomic_DNA.
DR EMBL; AP006241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140813; AAI40814.1; -; mRNA.
DR EMBL; BC144621; AAI44622.1; -; mRNA.
DR EMBL; AB208866; BAD92103.1; -; mRNA.
DR CCDS; CCDS46796.1; -. [Q14524-1]
DR CCDS; CCDS46797.1; -. [Q14524-2]
DR CCDS; CCDS46798.1; -. [Q14524-6]
DR CCDS; CCDS46799.1; -. [Q14524-4]
DR CCDS; CCDS54569.1; -. [Q14524-5]
DR CCDS; CCDS54570.1; -. [Q14524-3]
DR PIR; A38195; A38195.
DR RefSeq; NP_000326.2; NM_000335.4. [Q14524-2]
DR RefSeq; NP_001092874.1; NM_001099404.1.
DR RefSeq; NP_001092875.1; NM_001099405.1.
DR RefSeq; NP_001153632.1; NM_001160160.1.
DR RefSeq; NP_001153633.1; NM_001160161.1.
DR RefSeq; NP_932173.1; NM_198056.2. [Q14524-1]
DR PDB; 2KBI; NMR; -; A=1773-1865.
DR PDB; 2L53; NMR; -; B=1901-1927.
DR PDB; 4DCK; X-ray; 2.20 A; A=1773-1940.
DR PDB; 4DJC; X-ray; 1.35 A; B=1491-1522.
DR PDB; 4JQ0; X-ray; 3.84 A; D=1773-1940.
DR PDB; 4OVN; X-ray; 2.80 A; F/G/H/I/J=1773-1929.
DR PDB; 5DBR; X-ray; 2.25 A; C=1483-1529.
DR PDB; 6LQA; EM; 3.30 A; B=1-2016.
DR PDB; 6MUD; X-ray; 2.69 A; B=1786-1922.
DR PDB; 7DTC; EM; 3.30 A; A=1-2016.
DR PDB; 7L83; NMR; -; A=1597-1633.
DR PDBsum; 2KBI; -.
DR PDBsum; 2L53; -.
DR PDBsum; 4DCK; -.
DR PDBsum; 4DJC; -.
DR PDBsum; 4JQ0; -.
DR PDBsum; 4OVN; -.
DR PDBsum; 5DBR; -.
DR PDBsum; 6LQA; -.
DR PDBsum; 6MUD; -.
DR PDBsum; 7DTC; -.
DR PDBsum; 7L83; -.
DR AlphaFoldDB; Q14524; -.
DR BMRB; Q14524; -.
DR SMR; Q14524; -.
DR BioGRID; 112236; 26.
DR CORUM; Q14524; -.
DR DIP; DIP-38416N; -.
DR DIP; DIP-46144N; -.
DR IntAct; Q14524; 24.
DR MINT; Q14524; -.
DR STRING; 9606.ENSP00000410257; -.
DR BindingDB; Q14524; -.
DR ChEMBL; CHEMBL1980; -.
DR DrugBank; DB01426; Ajmaline.
DR DrugBank; DB09088; Amylocaine.
DR DrugBank; DB01429; Aprindine.
DR DrugBank; DB00868; Benzonatate.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB00527; Cinchocaine.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB13269; Dichlorobenzyl alcohol.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB01228; Encainide.
DR DrugBank; DB00754; Ethotoin.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB01195; Flecainide.
DR DrugBank; DB01320; Fosphenytoin.
DR DrugBank; DB00473; Hexylcaine.
DR DrugBank; DB00192; Indecainide.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB00281; Lidocaine.
DR DrugBank; DB00532; Mephenytoin.
DR DrugBank; DB00379; Mexiletine.
DR DrugBank; DB00680; Moricizine.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB11186; Pentoxyverine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB09345; Pramocaine.
DR DrugBank; DB00750; Prilocaine.
DR DrugBank; DB01035; Procainamide.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB01182; Propafenone.
DR DrugBank; DB09342; Propoxycaine.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB01346; Quinidine barbiturate.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00740; Riluzole.
DR DrugBank; DB09085; Tetracaine.
DR DrugBank; DB01056; Tocainide.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB06217; Vernakalant.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; Q14524; -.
DR GuidetoPHARMACOLOGY; 582; -.
DR TCDB; 1.A.1.10.3; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q14524; 15 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q14524; -.
DR PhosphoSitePlus; Q14524; -.
DR SwissPalm; Q14524; -.
DR BioMuta; SCN5A; -.
DR DMDM; 215273881; -.
DR jPOST; Q14524; -.
DR MassIVE; Q14524; -.
DR PaxDb; Q14524; -.
DR PeptideAtlas; Q14524; -.
DR PRIDE; Q14524; -.
DR ProteomicsDB; 18105; -.
DR ProteomicsDB; 60021; -. [Q14524-1]
DR ProteomicsDB; 60022; -. [Q14524-2]
DR ProteomicsDB; 60023; -. [Q14524-3]
DR ProteomicsDB; 60024; -. [Q14524-4]
DR ProteomicsDB; 60025; -. [Q14524-5]
DR ProteomicsDB; 60026; -. [Q14524-6]
DR ABCD; Q14524; 4 sequenced antibodies.
DR Antibodypedia; 6411; 319 antibodies from 32 providers.
DR DNASU; 6331; -.
DR Ensembl; ENST00000333535.9; ENSP00000328968.4; ENSG00000183873.18. [Q14524-1]
DR Ensembl; ENST00000423572.7; ENSP00000398266.2; ENSG00000183873.18. [Q14524-2]
DR GeneID; 6331; -.
DR KEGG; hsa:6331; -.
DR MANE-Select; ENST00000423572.7; ENSP00000398266.2; NM_000335.5; NP_000326.2. [Q14524-2]
DR UCSC; uc062ihe.1; human. [Q14524-1]
DR CTD; 6331; -.
DR DisGeNET; 6331; -.
DR GeneCards; SCN5A; -.
DR GeneReviews; SCN5A; -.
DR HGNC; HGNC:10593; SCN5A.
DR HPA; ENSG00000183873; Tissue enriched (heart).
DR MalaCards; SCN5A; -.
DR MIM; 108770; phenotype.
DR MIM; 113900; phenotype.
DR MIM; 272120; phenotype.
DR MIM; 600163; gene.
DR MIM; 601144; phenotype.
DR MIM; 601154; phenotype.
DR MIM; 603829; phenotype.
DR MIM; 603830; phenotype.
DR MIM; 608567; phenotype.
DR MIM; 614022; phenotype.
DR neXtProt; NX_Q14524; -.
DR OpenTargets; ENSG00000183873; -.
DR Orphanet; 1344; Atrial standstill.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 871; Familial progressive cardiac conduction defect.
DR Orphanet; 166282; Familial sick sinus syndrome.
DR Orphanet; 228140; Idiopathic ventricular fibrillation, non Brugada type.
DR Orphanet; 101016; Romano-Ward syndrome.
DR PharmGKB; PA304; -.
DR VEuPathDB; HostDB:ENSG00000183873; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000161691; -.
DR InParanoid; Q14524; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q14524; -.
DR PathwayCommons; Q14524; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; Q14524; -.
DR SIGNOR; Q14524; -.
DR BioGRID-ORCS; 6331; 15 hits in 1073 CRISPR screens.
DR ChiTaRS; SCN5A; human.
DR EvolutionaryTrace; Q14524; -.
DR GeneWiki; Nav1.5; -.
DR GenomeRNAi; 6331; -.
DR Pharos; Q14524; Tclin.
DR PRO; PR:Q14524; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14524; protein.
DR Bgee; ENSG00000183873; Expressed in apex of heart and 111 other tissues.
DR ExpressionAtlas; Q14524; baseline and differential.
DR Genevisible; Q14524; HS.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0016328; C:lateral plasma membrane; TAS:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0030506; F:ankyrin binding; IDA:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IPI:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0017134; F:fibroblast growth factor binding; IPI:BHF-UCL.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0086060; F:voltage-gated sodium channel activity involved in AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086061; F:voltage-gated sodium channel activity involved in bundle of His cell action potential; IMP:BHF-UCL.
DR GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IDA:BHF-UCL.
DR GO; GO:0086062; F:voltage-gated sodium channel activity involved in Purkinje myocyte action potential; IMP:BHF-UCL.
DR GO; GO:0086063; F:voltage-gated sodium channel activity involved in SA node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086016; P:AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086067; P:AV node cell to bundle of His cell communication; IMP:BHF-UCL.
DR GO; GO:0003360; P:brainstem development; ISS:BHF-UCL.
DR GO; GO:0086043; P:bundle of His cell action potential; IMP:BHF-UCL.
DR GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0003231; P:cardiac ventricle development; ISS:BHF-UCL.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; ISS:BHF-UCL.
DR GO; GO:0051899; P:membrane depolarization; IDA:BHF-UCL.
DR GO; GO:0086010; P:membrane depolarization during action potential; IDA:BHF-UCL.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; IMP:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; IMP:BHF-UCL.
DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; IMP:BHF-UCL.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:BHF-UCL.
DR GO; GO:0045760; P:positive regulation of action potential; ISS:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:BHF-UCL.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:BHF-UCL.
DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IMP:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL.
DR GO; GO:0086015; P:SA node cell action potential; IMP:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; IDA:UniProtKB.
DR GO; GO:0021537; P:telencephalon development; ISS:BHF-UCL.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR008053; Na_channel_a5su.
DR InterPro; IPR001696; Na_channel_asu.
DR InterPro; IPR044564; Na_chnl_inactivation_gate.
DR InterPro; IPR010526; Na_trans_assoc.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR Pfam; PF06512; Na_trans_assoc; 1.
DR Pfam; PF11933; Na_trans_cytopl; 1.
DR PRINTS; PR00170; NACHANNEL.
DR PRINTS; PR01666; NACHANNEL5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Atrial fibrillation; Brugada syndrome;
KW Calmodulin-binding; Cardiomyopathy; Cell membrane; Cytoplasm;
KW Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Long QT syndrome; Membrane; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW Voltage-gated channel.
FT CHAIN 1..2016
FT /note="Sodium channel protein type 5 subunit alpha"
FT /id="PRO_0000048497"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 132..150
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 151..157
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 158..178
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 179..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 193..210
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 211..216
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 217..233
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 234..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 253..272
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 273..357
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 358..382
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 383..389
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 390..410
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 411..717
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 718..736
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 737..747
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 748..767
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 768..781
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 782..801
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 802..803
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 804..821
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 822..837
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 838..856
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 857..883
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 884..904
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 905..917
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 918..938
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 939..1206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1207..1224
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1225..1237
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1238..1256
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1257..1270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1271..1289
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1290..1297
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1298..1316
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1317..1333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1334..1353
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1354..1405
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1406..1427
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1428..1444
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1445..1466
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1467..1529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1530..1547
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1548..1558
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1559..1577
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1578..1589
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1590..1607
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1608..1620
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1621..1637
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1638..1656
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1657..1674
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1675..1696
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1697..1719
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1720..1748
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1749..1771
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1772..2016
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 113..420
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 699..969
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1187..1501
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1510..1807
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1901..1930
FT /note="IQ"
FT REGION 28..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1005..1141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1839..1901
FT /note="Interaction with FGF13"
FT /evidence="ECO:0000269|PubMed:22705208"
FT REGION 1959..2016
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1974..1977
FT /note="Interaction with NEDD4, NEDD4L and WWP2"
FT /evidence="ECO:0000269|PubMed:15548568"
FT COMPBIAS 480..503
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1054..1068
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1090..1118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1959..1994
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 486
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15389"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 510
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 513
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 513
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 526
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 526
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJV9"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23092124"
FT MOD_RES 680
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 680
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:21726068"
FT MOD_RES 1503
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:19666841"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 740
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 803
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 864
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1736
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 280..335
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 906..915
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VAR_SEQ 206..211
FT /note="TTEFVD -> VSENIK (in isoform 3, isoform 4, isoform 5
FT and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16115203, ECO:0000303|Ref.6"
FT /id="VSP_037477"
FT VAR_SEQ 1076
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12358675,
FT ECO:0000303|PubMed:12454206, ECO:0000303|PubMed:14500339,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037478"
FT VAR_SEQ 1077..1130
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16115203"
FT /id="VSP_037479"
FT VAR_SEQ 1416..1433
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_037480"
FT VAR_SEQ 1573..1604
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037481"
FT VARIANT 9
FT /note="G -> V (in LQT3; dbSNP:rs199473043)"
FT /evidence="ECO:0000269|PubMed:16922724"
FT /id="VAR_036660"
FT VARIANT 18
FT /note="R -> Q (in BRGDA1 and LQT3; unknown pathological
FT significance; dbSNP:rs41311087)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074312"
FT VARIANT 18
FT /note="R -> W (rare variant; found in a patient with long
FT QT syndrome; unknown pathological significance;
FT dbSNP:rs199473044)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_068325"
FT VARIANT 27
FT /note="R -> H (in BRGDA1 and LQT3; dbSNP:rs199473045)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_026341"
FT VARIANT 30
FT /note="E -> G (in LQT3; unknown pathological significance;
FT dbSNP:rs199473551)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074695"
FT VARIANT 34
FT /note="R -> C (in dbSNP:rs6791924)"
FT /evidence="ECO:0000269|PubMed:11997281,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283"
FT /id="VAR_026342"
FT VARIANT 34
FT /note="R -> H (in dbSNP:rs199473046)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074313"
FT VARIANT 43
FT /note="R -> Q (in LQT3; does not affect baseline kinetics
FT of sodium currents; causes an unusual hyperpolarizing shift
FT of the activation kinetics after lidocaine treatment;
FT dbSNP:rs199473047)"
FT /evidence="ECO:0000269|PubMed:18848812,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055159"
FT VARIANT 48
FT /note="E -> K (in LQT3; unknown pathological significance;
FT dbSNP:rs199473048)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074696"
FT VARIANT 52
FT /note="P -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473553)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074697"
FT VARIANT 53
FT /note="R -> Q (in LQT3; unknown pathological significance;
FT dbSNP:rs199473049)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074698"
FT VARIANT 70
FT /note="N -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473050)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074314"
FT VARIANT 84
FT /note="D -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473051)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074315"
FT VARIANT 93
FT /note="F -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473052)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074316"
FT VARIANT 94
FT /note="I -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473053)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074317"
FT VARIANT 95
FT /note="V -> I (in BRGDA1; dbSNP:rs199473054)"
FT /evidence="ECO:0000269|PubMed:17081365"
FT /id="VAR_055160"
FT VARIANT 104
FT /note="R -> G (in LQT3; unknown pathological significance;
FT dbSNP:rs199473055)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074699"
FT VARIANT 104
FT /note="R -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473554)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074318"
FT VARIANT 104
FT /note="R -> W (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473055)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074319"
FT VARIANT 109
FT /note="N -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473056)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074320"
FT VARIANT 115
FT /note="S -> G (in LQT3; unknown pathological significance;
FT dbSNP:rs199473057)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074700"
FT VARIANT 121
FT /note="R -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473058)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074321"
FT VARIANT 121
FT /note="R -> W (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473556)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074322"
FT VARIANT 125
FT /note="V -> L (in LQT3; dbSNP:rs199473059)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_068326"
FT VARIANT 126
FT /note="K -> E (in BRGDA1; dbSNP:rs185492581)"
FT /evidence="ECO:0000269|PubMed:12051963,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026343"
FT VARIANT 136
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473557)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074323"
FT VARIANT 138
FT /note="M -> I (in ATFB10; dbSNP:rs199473060)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055161"
FT VARIANT 146
FT /note="V -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473061)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074324"
FT VARIANT 161
FT /note="E -> K (in BRGDA1 and PFHB1A; dbSNP:rs199473062)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026344"
FT VARIANT 161
FT /note="E -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473062)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074325"
FT VARIANT 175
FT /note="K -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473063)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074326"
FT VARIANT 178
FT /note="A -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473065)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074327"
FT VARIANT 182
FT /note="C -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473066)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074328"
FT VARIANT 185
FT /note="A -> V (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473067)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074329"
FT VARIANT 187
FT /note="T -> I (in BRGDA1; loss of function;
FT dbSNP:rs199473558)"
FT /evidence="ECO:0000269|PubMed:16325048"
FT /id="VAR_026345"
FT VARIANT 204
FT /note="A -> V (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473559)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074330"
FT VARIANT 212
FT /note="L -> P (in LQT3; dbSNP:rs199473070)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_055162"
FT VARIANT 212
FT /note="L -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473070)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074331"
FT VARIANT 216
FT /note="S -> L (rare variant found in patients with atrial
FT fibrillation; unknown pathological significance;
FT dbSNP:rs41276525)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055163"
FT VARIANT 220
FT /note="T -> I (in SSS1 and BRGDA1; dbSNP:rs45620037)"
FT /evidence="ECO:0000269|PubMed:14523039,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_017670"
FT VARIANT 222
FT /note="R -> Q (in BRGDA1 and LQT3; dbSNP:rs45546039)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074332"
FT VARIANT 223
FT /note="V -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473560)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074333"
FT VARIANT 225
FT /note="R -> Q (in LQT3; dbSNP:rs199473071)"
FT /evidence="ECO:0000269|PubMed:16922724"
FT /id="VAR_036661"
FT VARIANT 225
FT /note="R -> W (in PFHB1A, BRGDA1 and LQT3;
FT dbSNP:rs199473072)"
FT /evidence="ECO:0000269|PubMed:12574143,
FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283"
FT /id="VAR_055164"
FT VARIANT 226
FT /note="A -> V (in BRGDA1; dbSNP:rs199473561)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026346"
FT VARIANT 230
FT /note="I -> V (in BRGDA1; dbSNP:rs199473074)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026347"
FT VARIANT 232
FT /note="V -> I (in BRGDA1; unknown pathological
FT significance; dbSNP:rs45471994)"
FT /evidence="ECO:0000269|PubMed:18599870,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055165"
FT VARIANT 240
FT /note="V -> M (in BRGDA1 and LQT3; dbSNP:rs199473076)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074334"
FT VARIANT 245
FT /note="Q -> K (in LQT3; dbSNP:rs199473077)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068327"
FT VARIANT 247
FT /note="V -> L (in LQT3; unknown pathological significance;
FT dbSNP:rs199473078)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074701"
FT VARIANT 270
FT /note="Q -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473079)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074335"
FT VARIANT 275
FT /note="N -> K (in LQT3; unknown pathological significance;
FT dbSNP:rs199473080)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074702"
FT VARIANT 276
FT /note="L -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473081)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074336"
FT VARIANT 278
FT /note="H -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473562)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074337"
FT VARIANT 282
FT /note="R -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473082)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074338"
FT VARIANT 282
FT /note="R -> H (in BRGDA1; dbSNP:rs199473083)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026348"
FT VARIANT 286
FT /note="A -> S (in dbSNP:rs61746118)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074339"
FT VARIANT 289
FT /note="G -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473084)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074703"
FT VARIANT 291
FT /note="N -> S (in dbSNP:rs199473563)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074340"
FT VARIANT 294
FT /note="V -> M (in BRGDA1; dbSNP:rs199473086)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026349"
FT VARIANT 298
FT /note="G -> S (in PFHB1A; also in irritable bowel syndrome;
FT results in reduction of whole cell current density and a
FT delay in channel activation kinetics without a change in
FT single-channel conductance; dbSNP:rs137854608)"
FT /evidence="ECO:0000269|PubMed:11804990,
FT ECO:0000269|PubMed:19056759"
FT /id="VAR_017671"
FT VARIANT 299
FT /note="L -> M (in dbSNP:rs199473087)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074341"
FT VARIANT 300
FT /note="V -> I (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473088)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074342"
FT VARIANT 315
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473564)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074343"
FT VARIANT 319
FT /note="G -> S (in BRGDA1; dbSNP:rs199473090)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026350"
FT VARIANT 320
FT /note="T -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473091)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074344"
FT VARIANT 325
FT /note="L -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473092)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_055166"
FT VARIANT 336
FT /note="P -> L (in BRGDA1; severe reduction of sodium
FT currents; dbSNP:rs199473093)"
FT /evidence="ECO:0000269|PubMed:17075016,
FT ECO:0000269|PubMed:20129283, ECO:0000269|Ref.6"
FT /id="VAR_055167"
FT VARIANT 340
FT /note="R -> W (in LQT3; unknown pathological significance;
FT dbSNP:rs199473094)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074704"
FT VARIANT 351
FT /note="G -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473095)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074345"
FT VARIANT 351
FT /note="G -> V (in BRGDA1; 7-fold current reduction;
FT dbSNP:rs199473095)"
FT /evidence="ECO:0000269|PubMed:12051963,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026351"
FT VARIANT 353
FT /note="T -> I (in BRGDA1; dbSNP:rs199473096)"
FT /evidence="ECO:0000269|PubMed:17198989"
FT /id="VAR_055168"
FT VARIANT 356
FT /note="D -> N (in BRGDA1; loss of function;
FT dbSNP:rs199473565)"
FT /evidence="ECO:0000269|PubMed:16325048,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026352"
FT VARIANT 367
FT /note="R -> C (in BRGDA1 and LQT3; express no current;
FT dbSNP:rs199473097)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026353"
FT VARIANT 367
FT /note="R -> H (in BRGDA1; express no current;
FT dbSNP:rs28937318)"
FT /evidence="ECO:0000269|PubMed:11823453,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_017672"
FT VARIANT 367
FT /note="R -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs28937318)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074346"
FT VARIANT 369
FT /note="M -> K (in BRGDA1; dbSNP:rs199473098)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026354"
FT VARIANT 370
FT /note="T -> M (in LQT3; unknown pathological significance;
FT dbSNP:rs199473099)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074705"
FT VARIANT 374
FT /note="W -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473566)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074347"
FT VARIANT 376
FT /note="R -> C (in dbSNP:rs199473100)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074348"
FT VARIANT 376
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; also found in patients with atrial
FT fibrillation; dbSNP:rs199473101)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055169"
FT VARIANT 386
FT /note="G -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473567)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074349"
FT VARIANT 386
FT /note="G -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473102)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074350"
FT VARIANT 393
FT /note="Missing (in BRGDA1)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026355"
FT VARIANT 396
FT /note="V -> A (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473103)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074351"
FT VARIANT 396
FT /note="V -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473104)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074352"
FT VARIANT 397
FT /note="I -> T (in LQT3; unknown pathological significance;
FT dbSNP:rs199473105)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074706"
FT VARIANT 404
FT /note="L -> Q (in LQT3; dbSNP:rs199473107)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068328"
FT VARIANT 406
FT /note="N -> K (in LQT3; dbSNP:rs199473108)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055170"
FT VARIANT 406
FT /note="N -> S (in BRGDA1; dbSNP:rs199473568)"
FT /id="VAR_055171"
FT VARIANT 409
FT /note="L -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473109)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074707"
FT VARIANT 411
FT /note="V -> M (in LQT3; dbSNP:rs72549410)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_068329"
FT VARIANT 413
FT /note="A -> E (in LQT3; unknown pathological significance;
FT dbSNP:rs199473569)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074708"
FT VARIANT 413
FT /note="A -> T (in LQT3; unknown pathological significance;
FT dbSNP:rs199473110)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074709"
FT VARIANT 428
FT /note="E -> K (in ATFB10; dbSNP:rs199473111)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055172"
FT VARIANT 429
FT /note="Missing (in LQT3; unknown pathological significance;
FT dbSNP:rs761375502)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074710"
FT VARIANT 439
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473570)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074353"
FT VARIANT 445
FT /note="H -> D (in ATFB10; dbSNP:rs199473112)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055173"
FT VARIANT 447
FT /note="A -> G (in dbSNP:rs199473113)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074354"
FT VARIANT 449
FT /note="T -> A (in dbSNP:rs199473571)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074355"
FT VARIANT 461
FT /note="L -> V (in dbSNP:rs41313697)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055174"
FT VARIANT 462
FT /note="E -> A (in LQT3; unknown pathological significance;
FT dbSNP:rs199473114)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074711"
FT VARIANT 462
FT /note="E -> K (in LQT3; dbSNP:rs199473572)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068330"
FT VARIANT 470
FT /note="N -> K (in ATFB10; dbSNP:rs199473115)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055175"
FT VARIANT 475
FT /note="R -> S (in dbSNP:rs199473116)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074356"
FT VARIANT 481
FT /note="R -> W (in dbSNP:rs144511230)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055176"
FT VARIANT 501
FT /note="D -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473117)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074357"
FT VARIANT 512
FT /note="T -> I (in PFHB1A; voltage-dependent activation and
FT inactivation of the I-512 channel is shifted negatively by
FT 8 to 9 mV and had enhanced slow activation and slower
FT recovery from inactivation commpared to the wild-type
FT channel; the double mutant R-558/I-512 channel shows that
FT R-558 eliminates the negative shift induced by I-512 but
FT only partially restores the kinetic abnormalities;
FT dbSNP:rs199473118)"
FT /evidence="ECO:0000269|PubMed:12569159"
FT /id="VAR_036662"
FT VARIANT 514
FT /note="G -> C (in BRGDA1 and PFHB1A; dbSNP:rs137854606)"
FT /evidence="ECO:0000269|PubMed:11234013,
FT ECO:0000269|PubMed:19251209"
FT /id="VAR_017673"
FT VARIANT 524
FT /note="S -> Y (in dbSNP:rs41313691)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_036663"
FT VARIANT 526
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs45627438)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074358"
FT VARIANT 530
FT /note="F -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473120)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074712"
FT VARIANT 532
FT /note="F -> C (in SIDS and BRGDA1; dbSNP:rs199473573)"
FT /evidence="ECO:0000269|PubMed:18596570,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055177"
FT VARIANT 535
FT /note="R -> Q (in LQT3; unknown pathological significance;
FT dbSNP:rs199473121)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074713"
FT VARIANT 543
FT /note="F -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473122)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074359"
FT VARIANT 552
FT /note="G -> R (in BRGDA1; dbSNP:rs3918389)"
FT /evidence="ECO:0000269|PubMed:12358675,
FT ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:16616735,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026356"
FT VARIANT 558
FT /note="H -> R (channels properties are similar to wild-
FT type; the double mutant R-558/I-512 channel shows that R-
FT 558 eliminates the negative shift induced by Ile-512 but
FT only partially restores the kinetic abnormalities; can
FT modulate the gating defects caused by Ala-2006 and other
FT mutations; dbSNP:rs1805124)"
FT /evidence="ECO:0000269|PubMed:11997281,
FT ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12454206,
FT ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:14500339,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18368697,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283,
FT ECO:0000269|PubMed:21109022, ECO:0000269|PubMed:23085483"
FT /id="VAR_008955"
FT VARIANT 567
FT /note="L -> Q (in BRGDA1; dbSNP:rs199473124)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026357"
FT VARIANT 568
FT /note="R -> H (in dbSNP:rs199473125)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074360"
FT VARIANT 569
FT /note="R -> W (in LQT3; unknown pathological significance;
FT dbSNP:rs199473576)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074714"
FT VARIANT 571
FT /note="S -> I (in LQT3; unknown pathological significance;
FT dbSNP:rs199473126)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074715"
FT VARIANT 572
FT /note="A -> D (in LQT3 and ATFB10; likely benign variant;
FT dbSNP:rs36210423)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:18378609"
FT /id="VAR_055178"
FT VARIANT 572
FT /note="A -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs184442491)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074716"
FT VARIANT 572
FT /note="A -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs36210423)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074717"
FT VARIANT 573
FT /note="Q -> E (in LQT3; unknown pathological significance;
FT dbSNP:rs199473127)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074718"
FT VARIANT 579
FT /note="G -> R (in LQT3; unknown pathological significance;
FT dbSNP:rs199473128)"
FT /evidence="ECO:0000269|PubMed:16414944,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074361"
FT VARIANT 586..587
FT /note="Missing (in LQT3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_055179"
FT VARIANT 592
FT /note="N -> K (in dbSNP:rs199473130)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074362"
FT VARIANT 596
FT /note="D -> G (in dbSNP:rs199473131)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074363"
FT VARIANT 601
FT /note="V -> A (in dbSNP:rs199473132)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074364"
FT VARIANT 615
FT /note="G -> E (in LQT3 and BRGDA1; drug-induced LQT
FT syndrome; dbSNP:rs12720452)"
FT /evidence="ECO:0000269|PubMed:11997281,
FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026358"
FT VARIANT 618
FT /note="L -> F (in dbSNP:rs45488304)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283"
FT /id="VAR_047360"
FT VARIANT 619
FT /note="L -> F (in LQT3 and BRGDA1; dbSNP:rs199473133)"
FT /evidence="ECO:0000269|PubMed:11997281,
FT ECO:0000269|PubMed:12673799, ECO:0000269|PubMed:20129283"
FT /id="VAR_015682"
FT VARIANT 620
FT /note="R -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473577)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074365"
FT VARIANT 632
FT /note="T -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473134)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074366"
FT VARIANT 637
FT /note="P -> L (in LQT3; dbSNP:rs199473135)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068331"
FT VARIANT 638
FT /note="G -> D (in dbSNP:rs199473578)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074367"
FT VARIANT 639
FT /note="G -> R (in LQT3; dbSNP:rs199473136)"
FT /evidence="ECO:0000269|PubMed:16922724,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_036664"
FT VARIANT 640
FT /note="P -> A (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473137)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074368"
FT VARIANT 647
FT /note="A -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs185638763)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074369"
FT VARIANT 648
FT /note="P -> L (in LQT3 and BRGDA1; dbSNP:rs45609733)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_068332"
FT VARIANT 654
FT /note="E -> K (in LQT3; unknown pathological significance;
FT dbSNP:rs199473138)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074719"
FT VARIANT 655
FT /note="E -> K (in ATFB10; dbSNP:rs199473579)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055180"
FT VARIANT 656
FT /note="P -> L (in dbSNP:rs41313681)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074370"
FT VARIANT 661
FT /note="R -> W (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473139)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074371"
FT VARIANT 672
FT /note="A -> T (in dbSNP:rs199473140)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074372"
FT VARIANT 673
FT /note="L -> P (in LQT3; unknown pathological significance;
FT dbSNP:rs199473141)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074720"
FT VARIANT 680
FT /note="R -> H (in LQT3; dbSNP:rs199473142)"
FT /id="VAR_055181"
FT VARIANT 681
FT /note="H -> P (in BRGDA1; dbSNP:rs199473143)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026359"
FT VARIANT 683
FT /note="C -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473144)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074373"
FT VARIANT 689
FT /note="R -> C (in LQT3; unknown pathological significance;
FT dbSNP:rs199473580)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074721"
FT VARIANT 689
FT /note="R -> H (in LQT3; unknown pathological significance;
FT dbSNP:rs199473145)"
FT /evidence="ECO:0000269|PubMed:16414944,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074374"
FT VARIANT 692
FT /note="Q -> K (in dbSNP:rs45553235)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074375"
FT VARIANT 701
FT /note="P -> L (in BRGDA1 and LQT3; dbSNP:rs199473147)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074376"
FT VARIANT 705
FT /note="S -> F (in dbSNP:rs199473148)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074377"
FT VARIANT 717
FT /note="P -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473149)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074378"
FT VARIANT 731
FT /note="T -> I (in LQT3; unknown pathological significance;
FT dbSNP:rs199473150)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074722"
FT VARIANT 735
FT /note="A -> E (in BRGDA1; dbSNP:rs137854611)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026360"
FT VARIANT 735
FT /note="A -> V (in BRGDA1 and SSS1; expresses currents with
FT steady state activation voltage shifted to more positive
FT potentials and exhibit reduced sodium channel current at
FT the end of phase I of the action potential;
FT dbSNP:rs137854611)"
FT /evidence="ECO:0000269|PubMed:11823453,
FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:22795782"
FT /id="VAR_017674"
FT VARIANT 746
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473582)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074379"
FT VARIANT 750
FT /note="Q -> R (in LQT3; unknown pathological significance;
FT dbSNP:rs199473152)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074723"
FT VARIANT 752
FT /note="G -> R (in BRGDA1 and PFHB1A; dbSNP:rs199473153)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026361"
FT VARIANT 758
FT /note="G -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473154)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074380"
FT VARIANT 764
FT /note="M -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473156)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074381"
FT VARIANT 772
FT /note="D -> N (in BRGDA1 and LQT3; dbSNP:rs199473157)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074382"
FT VARIANT 773
FT /note="P -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473158)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074383"
FT VARIANT 789
FT /note="V -> I (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473159)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074384"
FT VARIANT 808
FT /note="R -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473160)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074385"
FT VARIANT 812
FT /note="L -> Q (in BRGDA1; decreased protein abundance;
FT retained intracellularly; decreased voltage-gated sodium
FT channel activity; hyperpolarizing shift of the voltage
FT dependence of inactivation leading to reduced sodium window
FT current; no dominant negative effect)"
FT /evidence="ECO:0000269|PubMed:26279430"
FT /id="VAR_076555"
FT VARIANT 814
FT /note="R -> Q (in BRGDA1; dbSNP:rs199473584)"
FT /id="VAR_055182"
FT VARIANT 816
FT /note="F -> Y (in LQT3; unknown pathological significance;
FT dbSNP:rs199473162)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074724"
FT VARIANT 817
FT /note="K -> E (in BRGDA1; no effect on localization to the
FT plasma membrane; decreased voltage-gated sodium channel
FT activity; shift in the voltage dependence of activation and
FT changed recovery from inactivation)"
FT /evidence="ECO:0000269|PubMed:26776555"
FT /id="VAR_076556"
FT VARIANT 839
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473164)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074386"
FT VARIANT 848
FT /note="I -> F (in LQT3; unknown pathological significance;
FT dbSNP:rs199473166)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074725"
FT VARIANT 851
FT /note="F -> L (in BRGDA1; dbSNP:rs199473586)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026362"
FT VARIANT 867
FT /note="E -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473167)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074387"
FT VARIANT 878
FT /note="R -> C (in BRGDA1; dbSNP:rs199473168)"
FT /evidence="ECO:0000269|PubMed:18616619,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055183"
FT VARIANT 878
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473587)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074388"
FT VARIANT 886
FT /note="H -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473169)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074389"
FT VARIANT 892
FT /note="F -> I (in BRGDA1; dbSNP:rs199473170)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026363"
FT VARIANT 893
FT /note="R -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473171)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074390"
FT VARIANT 893
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473172)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074391"
FT VARIANT 896
FT /note="C -> S (in BRGDA1; dbSNP:rs199473173)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026364"
FT VARIANT 901
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473174)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074392"
FT VARIANT 910
FT /note="S -> L (in BRGDA1; dbSNP:rs199473175)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026365"
FT VARIANT 915
FT /note="C -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473588)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074393"
FT VARIANT 917
FT /note="L -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473176)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074394"
FT VARIANT 924
FT /note="V -> I (in dbSNP:rs199473177)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074395"
FT VARIANT 927
FT /note="N -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473589)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074396"
FT VARIANT 928
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473178)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074397"
FT VARIANT 935
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473179)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074398"
FT VARIANT 941
FT /note="S -> N (in LQT3; also in SIDS; dbSNP:rs137854605)"
FT /evidence="ECO:0000269|PubMed:10911008"
FT /id="VAR_017675"
FT VARIANT 960
FT /note="Q -> K (in LQT3; unknown pathological significance;
FT dbSNP:rs199473590)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074726"
FT VARIANT 965
FT /note="R -> C (in BRGDA1; steady state inactivation shifted
FT to a more negative potential; slower recovery from
FT inactivation; dbSNP:rs199473180)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:20129283"
FT /id="VAR_026366"
FT VARIANT 965
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473181)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074399"
FT VARIANT 965
FT /note="R -> L (in LQT3; unknown pathological significance;
FT dbSNP:rs199473181)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074727"
FT VARIANT 971
FT /note="R -> C (in LQT3; dbSNP:rs61737825)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068333"
FT VARIANT 981
FT /note="C -> F (in LQT3; unknown pathological significance;
FT dbSNP:rs199473591)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074728"
FT VARIANT 986
FT /note="R -> Q (in dbSNP:rs41313667)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074400"
FT VARIANT 997
FT /note="A -> S (in LQT3; also found in patients with atrial
FT fibrillation; sodium current characterized by slower decay
FT and a 2- to 3-fold increase in late sodium current;
FT dbSNP:rs137854609)"
FT /evidence="ECO:0000269|PubMed:11710892,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:19716085"
FT /id="VAR_017676"
FT VARIANT 997
FT /note="A -> T (in BRGDA1; unknown pathological
FT significance; dbSNP:rs137854609)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074401"
FT VARIANT 1004
FT /note="C -> R (in LQT3; unknown pathological significance;
FT dbSNP:rs199473183)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074729"
FT VARIANT 1016
FT /note="T -> M (in dbSNP:rs199473185)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074402"
FT VARIANT 1023
FT /note="R -> H (in BRGDA1; dbSNP:rs199473592)"
FT /id="VAR_055184"
FT VARIANT 1027
FT /note="R -> Q (in dbSNP:rs763891399)"
FT /evidence="ECO:0000269|PubMed:1309946,
FT ECO:0000269|PubMed:16616735, ECO:0000269|Ref.6"
FT /id="VAR_026367"
FT VARIANT 1040
FT /note="G -> R (in dbSNP:rs199473186)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074403"
FT VARIANT 1041
FT /note="D -> N (in dbSNP:rs45491996)"
FT /id="VAR_047361"
FT VARIANT 1053
FT /note="E -> K (in BRGDA1, ATFB10 and LQT3; abolishes
FT binding to ANK3 and also prevents accumulation of SCN5A at
FT cell surface sites in ventricular cardiomyocytes;
FT dbSNP:rs137854617)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283"
FT /id="VAR_026368"
FT VARIANT 1055
FT /note="D -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473593)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074404"
FT VARIANT 1069
FT /note="T -> M (in LQT3; dbSNP:rs199473187)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_068334"
FT VARIANT 1079
FT /note="S -> Y (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473188)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074405"
FT VARIANT 1082
FT /note="V -> A (in dbSNP:rs199473189)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074406"
FT VARIANT 1084
FT /note="G -> S (in SIDS; unknown pathological significance;
FT dbSNP:rs199473190)"
FT /evidence="ECO:0000269|PubMed:18596570"
FT /id="VAR_055185"
FT VARIANT 1090
FT /note="P -> L (in dbSNP:rs1805125)"
FT /evidence="ECO:0000269|PubMed:18368697,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_014464"
FT VARIANT 1098
FT /note="V -> L (in dbSNP:rs199473191)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074407"
FT VARIANT 1100
FT /note="A -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473192)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074730"
FT VARIANT 1103
FT /note="S -> Y (may confer susceptibility to acquired
FT arrhythmia; dbSNP:rs7626962)"
FT /evidence="ECO:0000269|PubMed:12193783,
FT ECO:0000269|PubMed:12471205, ECO:0000269|PubMed:14500339,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283"
FT /id="VAR_017677"
FT VARIANT 1107
FT /note="E -> K (in dbSNP:rs199473193)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074408"
FT VARIANT 1113
FT /note="A -> V (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473194)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074409"
FT VARIANT 1114
FT /note="D -> N (in LQT3; dbSNP:rs199473195)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_009935"
FT VARIANT 1116
FT /note="R -> W (in dbSNP:rs199473196)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074410"
FT VARIANT 1131
FT /note="T -> I (in ATFB10; dbSNP:rs199473197)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055186"
FT VARIANT 1140
FT /note="S -> T (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473199)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074411"
FT VARIANT 1166
FT /note="D -> N (in LQT3; unknown pathological significance;
FT dbSNP:rs199473594)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074731"
FT VARIANT 1180
FT /note="A -> V (in dbSNP:rs41310765)"
FT /id="VAR_047362"
FT VARIANT 1193
FT /note="R -> Q (in BRGDA1 and LQT3; also found in patients
FT with atrial fibrillation; accelerates the inactivation of
FT the sodium channel current and exhibit reduced sodium
FT channel current at the end of phase I of the action
FT potential; dbSNP:rs41261344)"
FT /evidence="ECO:0000269|PubMed:11823453,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283"
FT /id="VAR_017678"
FT VARIANT 1199
FT /note="Y -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473202)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074732"
FT VARIANT 1212
FT /note="Missing (in LQT3; unknown pathological significance;
FT dbSNP:rs794728920)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074733"
FT VARIANT 1219
FT /note="S -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473597)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074412"
FT VARIANT 1225
FT /note="E -> K (in BRGDA1 and LQT3; dbSNP:rs199473204)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:20129283"
FT /id="VAR_026369"
FT VARIANT 1228
FT /note="Y -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473205)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074413"
FT VARIANT 1231
FT /note="E -> K (in LQT3; dbSNP:rs199473598)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068335"
FT VARIANT 1232
FT /note="R -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473206)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074414"
FT VARIANT 1232
FT /note="R -> W (in BRGDA1 and PFHB1A; dbSNP:rs199473207)"
FT /evidence="ECO:0000269|PubMed:19251209,
FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:9521325"
FT /id="VAR_017679"
FT VARIANT 1236
FT /note="K -> N (in BRGDA1; dbSNP:rs199473208)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026370"
FT VARIANT 1239
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473210)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074415"
FT VARIANT 1240
FT /note="E -> Q (in dbSNP:rs199473211)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026371"
FT VARIANT 1243
FT /note="D -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473599)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074416"
FT VARIANT 1249
FT /note="V -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473213)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074417"
FT VARIANT 1250
FT /note="F -> L (in LQT3; drug-induced LQT syndrome;
FT dbSNP:rs45589741)"
FT /evidence="ECO:0000269|PubMed:11997281"
FT /id="VAR_026372"
FT VARIANT 1251
FT /note="V -> M (in dbSNP:rs199473600)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074418"
FT VARIANT 1253
FT /note="E -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473214)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074419"
FT VARIANT 1262
FT /note="G -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs137854616)"
FT /evidence="ECO:0000269|PubMed:15338453,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_036665"
FT VARIANT 1271
FT /note="W -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473601)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074420"
FT VARIANT 1275
FT /note="D -> N (in CMD1E, BRGDA1, PFHB1A and ATRST1; in
FT familial atrial standstill is found in association with
FT variants in the regulatory region of GJA5; decreases
FT expression at the cell membrane; alters channel kinetics;
FT shifts activation and inactivation to more positive
FT membrane potentials; dbSNP:rs137854618)"
FT /evidence="ECO:0000269|PubMed:12522116,
FT ECO:0000269|PubMed:15466643, ECO:0000269|PubMed:19251209,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026373"
FT VARIANT 1283
FT /note="L -> M (in LQT3; unknown pathological significance;
FT dbSNP:rs199473216)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074734"
FT VARIANT 1288
FT /note="A -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473217)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074421"
FT VARIANT 1293
FT /note="F -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs41311127)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026374"
FT VARIANT 1295
FT /note="E -> K (in LQT3; causes significant positive shifts
FT in the half-maximal voltage of steady-state inactivation
FT and activation; dbSNP:rs199473218)"
FT /evidence="ECO:0000269|PubMed:11304498"
FT /id="VAR_055187"
FT VARIANT 1298
FT /note="P -> L (in SSS1; dbSNP:rs28937319)"
FT /evidence="ECO:0000269|PubMed:14523039"
FT /id="VAR_017680"
FT VARIANT 1304
FT /note="T -> M (in LQT3; dbSNP:rs199473603)"
FT /evidence="ECO:0000269|PubMed:10508990,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_008956"
FT VARIANT 1308
FT /note="L -> F (associated with I-232 in a case of
FT lidocaine-induced Brugada syndrome; dbSNP:rs41313031)"
FT /evidence="ECO:0000269|PubMed:18599870,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_055188"
FT VARIANT 1311
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473219)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074422"
FT VARIANT 1319
FT /note="G -> V (in BRGDA1; dbSNP:rs199473220)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026375"
FT VARIANT 1323
FT /note="V -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473221)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074423"
FT VARIANT 1325
FT /note="N -> S (in LQT3; dbSNP:rs28937317)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_001577"
FT VARIANT 1326
FT /note="A -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473222)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074735"
FT VARIANT 1330
FT /note="A -> P (in LQT3; dbSNP:rs199473224)"
FT /id="VAR_055189"
FT VARIANT 1330
FT /note="A -> T (in LQT3; dbSNP:rs199473224)"
FT /id="VAR_055190"
FT VARIANT 1332
FT /note="P -> L (in LQT3 and BRGDA1; unknown pathological
FT significance; dbSNP:rs199473225)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_055191"
FT VARIANT 1333
FT /note="S -> Y (in LQT3 and SIDS; dbSNP:rs199473604)"
FT /evidence="ECO:0000269|PubMed:16922724,
FT ECO:0000269|PubMed:19302788"
FT /id="VAR_036666"
FT VARIANT 1334
FT /note="I -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473226)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074736"
FT VARIANT 1338
FT /note="L -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473227)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074737"
FT VARIANT 1344
FT /note="F -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473228)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074424"
FT VARIANT 1344
FT /note="F -> S (in BRGDA1; dbSNP:rs199473229)"
FT /evidence="ECO:0000269|PubMed:16616735"
FT /id="VAR_026376"
FT VARIANT 1346
FT /note="L -> I (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473230)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074425"
FT VARIANT 1346
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473231)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074426"
FT VARIANT 1351
FT /note="M -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473232)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074427"
FT VARIANT 1353
FT /note="V -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473233)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074428"
FT VARIANT 1358
FT /note="G -> W (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473234)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074429"
FT VARIANT 1359
FT /note="K -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473235)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074430"
FT VARIANT 1360
FT /note="F -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473236)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074431"
FT VARIANT 1363
FT /note="C -> Y (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473237)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074432"
FT VARIANT 1382
FT /note="S -> I (in BRGDA1; dbSNP:rs199473608)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026377"
FT VARIANT 1405
FT /note="V -> L (in BRGDA1; dbSNP:rs199473239)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026378"
FT VARIANT 1405
FT /note="V -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473239)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074433"
FT VARIANT 1406
FT /note="G -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473609)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074434"
FT VARIANT 1406
FT /note="G -> R (in BRGDA1; dbSNP:rs199473240)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_026379"
FT VARIANT 1408
FT /note="G -> R (in SSS1 and BRGDA1; dbSNP:rs137854612)"
FT /evidence="ECO:0000269|PubMed:11748104,
FT ECO:0000269|PubMed:14523039, ECO:0000269|PubMed:19251209,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_017681"
FT VARIANT 1409
FT /note="Y -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473610)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074435"
FT VARIANT 1412
FT /note="L -> F (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473241)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074436"
FT VARIANT 1419
FT /note="K -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473242)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074437"
FT VARIANT 1420
FT /note="G -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473611)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074438"
FT VARIANT 1427
FT /note="A -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473244)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074439"
FT VARIANT 1428
FT /note="A -> V (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473612)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074440"
FT VARIANT 1432
FT /note="R -> G (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473245)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_055192"
FT VARIANT 1432
FT /note="R -> S (in BRGDA1 and LQT3; dbSNP:rs199473246)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074441"
FT VARIANT 1433
FT /note="G -> V (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473247)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074442"
FT VARIANT 1438
FT /note="P -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473248)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_055193"
FT VARIANT 1441
FT /note="E -> Q (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473249)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074443"
FT VARIANT 1448
FT /note="I -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473250)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074444"
FT VARIANT 1448
FT /note="I -> T (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473251)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074445"
FT VARIANT 1449
FT /note="Y -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473613)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074446"
FT VARIANT 1451
FT /note="V -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473252)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074447"
FT VARIANT 1458
FT /note="S -> Y (in LQT3; dbSNP:rs199473253)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068336"
FT VARIANT 1463
FT /note="N -> Y (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473614)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074448"
FT VARIANT 1468
FT /note="V -> F (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473254)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074449"
FT VARIANT 1472
FT /note="N -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473255)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074738"
FT VARIANT 1473
FT /note="F -> C (in LQT3; dbSNP:rs199473256)"
FT /evidence="ECO:0000269|PubMed:18060054,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055194"
FT VARIANT 1479
FT /note="Missing (in BRGDA1)"
FT /evidence="ECO:0000269|PubMed:12106943"
FT /id="VAR_026380"
FT VARIANT 1481
FT /note="G -> E (in LQT3; dbSNP:rs199473257)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_068337"
FT VARIANT 1486
FT /note="F -> L (in LQT3; dbSNP:rs199473615)"
FT /id="VAR_055195"
FT VARIANT 1487
FT /note="M -> L (in LQT3; unknown pathological significance;
FT dbSNP:rs199473258)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074739"
FT VARIANT 1488
FT /note="T -> R (in LQT3; unknown pathological significance;
FT dbSNP:rs199473259)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074740"
FT VARIANT 1489
FT /note="E -> D (in LQT3; unknown pathological significance;
FT dbSNP:rs199473616)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074741"
FT VARIANT 1493
FT /note="K -> R (in LQT3; unknown pathological significance;
FT dbSNP:rs199473260)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074742"
FT VARIANT 1494
FT /note="Y -> N (in BRGDA1; dbSNP:rs199473261)"
FT /evidence="ECO:0000269|PubMed:18341814"
FT /id="VAR_055196"
FT VARIANT 1495
FT /note="Y -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473262)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074743"
FT VARIANT 1498
FT /note="M -> T (found in a patient with long QT syndrome;
FT unknown pathological significance; dbSNP:rs199473263)"
FT /evidence="ECO:0000269|PubMed:16115203,
FT ECO:0000269|PubMed:16414944"
FT /id="VAR_074744"
FT VARIANT 1498
FT /note="M -> V (in LQT3; unknown pathological significance;
FT dbSNP:rs199473264)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074745"
FT VARIANT 1500
FT /note="K -> N (in dbSNP:rs199473265)"
FT /evidence="ECO:0000269|PubMed:10508990"
FT /id="VAR_008957"
FT VARIANT 1500
FT /note="Missing (in BRGDA1)"
FT /evidence="ECO:0000269|PubMed:11901046"
FT /id="VAR_026381"
FT VARIANT 1501
FT /note="L -> V (in LQT3 and BRGDA1; dbSNP:rs199473266)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283"
FT /id="VAR_009936"
FT VARIANT 1502
FT /note="G -> S (in BRGDA1; dbSNP:rs199473267)"
FT /evidence="ECO:0000269|PubMed:12106943"
FT /id="VAR_026382"
FT VARIANT 1505..1507
FT /note="Missing (in LQT3)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:7651517"
FT /id="VAR_001576"
FT VARIANT 1505
FT /note="K -> N (in LQT3; unknown pathological significance;
FT dbSNP:rs199473268)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074746"
FT VARIANT 1507..1509
FT /note="Missing (in LQT3)"
FT /id="VAR_055197"
FT VARIANT 1512
FT /note="R -> W (in BRGDA1; significantly affects cardiac
FT sodium channel characteristics; associated with an increase
FT in inward sodium current during the action potential
FT upstroke; dbSNP:rs137854602)"
FT /evidence="ECO:0000269|PubMed:10690282,
FT ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:19251209,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_017682"
FT VARIANT 1521
FT /note="I -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473617)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074450"
FT VARIANT 1525
FT /note="V -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473269)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074451"
FT VARIANT 1527
FT /note="K -> R (in BRGDA1; asymptomatic patient; associated
FT with P-1569; dbSNP:rs199473270)"
FT /evidence="ECO:0000269|PubMed:15851320"
FT /id="VAR_055198"
FT VARIANT 1532
FT /note="V -> I (in LQT3; unknown pathological significance;
FT dbSNP:rs199473618)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074747"
FT VARIANT 1548
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473271)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074452"
FT VARIANT 1560
FT /note="L -> F (in LQT3; unknown pathological significance;
FT dbSNP:rs199473619)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074748"
FT VARIANT 1569
FT /note="A -> P (in BRGDA1; asymptomatic patient; associated
FT with R-1527; dbSNP:rs199473273)"
FT /evidence="ECO:0000269|PubMed:15851320"
FT /id="VAR_055199"
FT VARIANT 1571
FT /note="F -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473274)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074453"
FT VARIANT 1571
FT /note="F -> L (in BRGDA1; affects channel activity; the
FT mutant displays a hyperpolarizing shift in the voltage
FT dependence of inactivation causing slower inactivation
FT compared to the wild type, slower recovery and a reduced
FT availability of channels at rest)"
FT /evidence="ECO:0000269|PubMed:32850980"
FT /id="VAR_085793"
FT VARIANT 1574
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473620)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074454"
FT VARIANT 1582
FT /note="L -> P (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473275)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074455"
FT VARIANT 1583
FT /note="R -> C (in BRGDA1; unknown pathological
FT significance; dbSNP:rs45514691)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074456"
FT VARIANT 1583
FT /note="R -> H (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473621)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074457"
FT VARIANT 1593
FT /note="I -> M (in LQT3; unknown pathological significance;
FT dbSNP:rs199473276)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074749"
FT VARIANT 1594
FT /note="F -> S (in LQT3; unknown pathological significance;
FT dbSNP:rs199473277)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074750"
FT VARIANT 1595
FT /note="D -> N (in PFHB1A; significant defect in the
FT kinetics of fast-channel inactivation distinct from
FT mutations reported in LQT3; dbSNP:rs137854607)"
FT /evidence="ECO:0000269|PubMed:11804990"
FT /id="VAR_017683"
FT VARIANT 1596
FT /note="F -> I (in LQT3; unknown pathological significance;
FT dbSNP:rs199473278)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074751"
FT VARIANT 1604
FT /note="V -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473280)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074458"
FT VARIANT 1609
FT /note="S -> W (in LQT3; dbSNP:rs199473622)"
FT /evidence="ECO:0000269|PubMed:16922724"
FT /id="VAR_036667"
FT VARIANT 1613
FT /note="Q -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473281)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074459"
FT VARIANT 1617
FT /note="Missing (in LQT3 and BRGDA1)"
FT /evidence="ECO:0000269|PubMed:17081365,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055200"
FT VARIANT 1620
FT /note="T -> K (in LQT3 and PFHB1A; dbSNP:rs199473282)"
FT /id="VAR_055201"
FT VARIANT 1620
FT /note="T -> M (in BRGDA1; arrhythmogenicity revealed only
FT at temperatures approaching the physiologic range;
FT dbSNP:rs199473282)"
FT /evidence="ECO:0000269|PubMed:10532948,
FT ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:20129283,
FT ECO:0000269|PubMed:9521325"
FT /id="VAR_017684"
FT VARIANT 1623
FT /note="R -> L (in LQT3; dbSNP:rs137854600)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:19716085"
FT /id="VAR_009937"
FT VARIANT 1623
FT /note="R -> Q (in LQT3 and BRGDA1; dbSNP:rs137854600)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:9506831,
FT ECO:0000269|Ref.35"
FT /id="VAR_001578"
FT VARIANT 1626
FT /note="R -> H (in LQT3; unknown pathological significance;
FT dbSNP:rs199473283)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074752"
FT VARIANT 1626
FT /note="R -> P (in LQT3; unknown pathological significance;
FT dbSNP:rs199473283)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_055202"
FT VARIANT 1629
FT /note="R -> Q (in BRGDA1; changed voltage-gated sodium
FT channel activity; no difference in current density but
FT changed inactivation kinetics and prolonged recovery from
FT inactivation; dbSNP:rs199473623)"
FT /evidence="ECO:0000269|PubMed:20129283,
FT ECO:0000269|PubMed:24167619"
FT /id="VAR_074460"
FT VARIANT 1642
FT /note="G -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473624)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074461"
FT VARIANT 1644
FT /note="R -> C (in LQT3 and BRGDA1; dbSNP:rs199473287)"
FT /evidence="ECO:0000269|PubMed:16414944,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055203"
FT VARIANT 1644
FT /note="R -> H (in LQT3; dbSNP:rs28937316)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:15840476"
FT /id="VAR_001579"
FT VARIANT 1645
FT /note="T -> M (in LQT3; dbSNP:rs199473288)"
FT /evidence="ECO:0000269|PubMed:10508990"
FT /id="VAR_008958"
FT VARIANT 1649
FT /note="A -> V (in BRGDA1; dbSNP:rs199473289)"
FT /evidence="ECO:0000269|PubMed:17081365"
FT /id="VAR_055204"
FT VARIANT 1650
FT /note="L -> F (in LQT3; unknown pathological significance;
FT dbSNP:rs199473290)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074753"
FT VARIANT 1652
FT /note="M -> R (in LQT3; dbSNP:rs199473291)"
FT /id="VAR_055205"
FT VARIANT 1652
FT /note="M -> T (in LQT3; unknown pathological significance;
FT dbSNP:rs199473291)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074754"
FT VARIANT 1660
FT /note="I -> V (in BRGDA1 and LQT3; complete loss of sodium
FT currents due to defective channel trafficking to the plasma
FT membrane; dbSNP:rs199473625)"
FT /evidence="ECO:0000269|PubMed:16414944,
FT ECO:0000269|PubMed:17075016, ECO:0000269|PubMed:20129283"
FT /id="VAR_055206"
FT VARIANT 1661
FT /note="G -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473292)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074462"
FT VARIANT 1667
FT /note="V -> I (in LQT3 and BRGDA1; dbSNP:rs199473293)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_068338"
FT VARIANT 1672
FT /note="S -> Y (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473626)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074463"
FT VARIANT 1680
FT /note="A -> T (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473294)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074464"
FT VARIANT 1690
FT /note="D -> N (in BRGDA1; decreased localization to the
FT plasma membrane; decreased voltage-gated sodium channel
FT activity; dominant negative effect; no effect on voltage
FT dependence for activation and inactivation;
FT dbSNP:rs1060499900)"
FT /evidence="ECO:0000269|PubMed:23085483"
FT /id="VAR_076557"
FT VARIANT 1698
FT /note="A -> T (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473295)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074465"
FT VARIANT 1705
FT /note="F -> S (in SIDS; causes a hyperpolarizing shift of
FT steady-state inactivation and delayed recovery from
FT inactivation; dbSNP:rs199473627)"
FT /evidence="ECO:0000269|PubMed:18596570"
FT /id="VAR_055207"
FT VARIANT 1709
FT /note="T -> M (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473297)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074466"
FT VARIANT 1709
FT /note="T -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473297)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074467"
FT VARIANT 1710
FT /note="S -> L (in VF1; dbSNP:rs137854604)"
FT /evidence="ECO:0000269|PubMed:10940383"
FT /id="VAR_017685"
FT VARIANT 1712
FT /note="G -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473298)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074468"
FT VARIANT 1714
FT /note="D -> G (in BRGDA1; strong decrease of current
FT density; does not affect ion selectivity properties;
FT dbSNP:rs199473628)"
FT /evidence="ECO:0000269|PubMed:16266370,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026383"
FT VARIANT 1722
FT /note="N -> D (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473299)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074469"
FT VARIANT 1723
FT /note="T -> N (in LQT3; unknown pathological significance;
FT dbSNP:rs199473300)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074755"
FT VARIANT 1728
FT /note="C -> R (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473302)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074470"
FT VARIANT 1728
FT /note="C -> W (in BRGDA1; unknown pathological
FT significance; dbSNP:rs193922726)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074471"
FT VARIANT 1739
FT /note="R -> W (in LQT3; unknown pathological significance;
FT dbSNP:rs199473303)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074756"
FT VARIANT 1740
FT /note="G -> R (in BRGDA1; dbSNP:rs199473304)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026384"
FT VARIANT 1743
FT /note="G -> E (in BRGDA1; dbSNP:rs199473629)"
FT /evidence="ECO:0000269|PubMed:12106943,
FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283"
FT /id="VAR_026385"
FT VARIANT 1743
FT /note="G -> R (in BRGDA1; decreases expression at the cell
FT membrane; yields nearly undetectable currents in
FT transfected cells; dbSNP:rs199473305)"
FT /evidence="ECO:0000269|PubMed:15023552,
FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:23420830"
FT /id="VAR_055208"
FT VARIANT 1748
FT /note="G -> D (in BRGDA1; decreased localization to the
FT plasma membrane; decreased voltage-gated sodium channel
FT activity; dominant negative effect; changed voltage
FT dependence for activation and inactivation)"
FT /evidence="ECO:0000269|PubMed:23085483"
FT /id="VAR_076558"
FT VARIANT 1761
FT /note="L -> F (in LQT3; unknown pathological significance;
FT dbSNP:rs199473307)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074757"
FT VARIANT 1761
FT /note="L -> H (in LQT3; unknown pathological significance;
FT dbSNP:rs199473308)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074758"
FT VARIANT 1763
FT /note="V -> M (in LQT3; dbSNP:rs199473631)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055209"
FT VARIANT 1764
FT /note="V -> F (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473309)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074472"
FT VARIANT 1766
FT /note="M -> L (in LQT3; affects protein trafficking;
FT dbSNP:rs199473310)"
FT /evidence="ECO:0000269|PubMed:12454206,
FT ECO:0000269|PubMed:15840476"
FT /id="VAR_055210"
FT VARIANT 1767
FT /note="Y -> C (in LQT3; unknown pathological significance;
FT dbSNP:rs199473632)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074759"
FT VARIANT 1768
FT /note="I -> V (in LQT3; increases the rate of recovery from
FT inactivation and the channel availability, observed as a
FT positive shift of the steady-state inactivation curve;
FT dbSNP:rs199473311)"
FT /evidence="ECO:0000269|PubMed:12209021"
FT /id="VAR_055211"
FT VARIANT 1777
FT /note="V -> M (in LQT3; dbSNP:rs199473314)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_055212"
FT VARIANT 1779
FT /note="T -> M (in LQT3 and BRGDA1; dbSNP:rs199473634)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283"
FT /id="VAR_068339"
FT VARIANT 1784
FT /note="E -> K (in LQT3 and BRGDA1; dbSNP:rs137854601)"
FT /evidence="ECO:0000269|PubMed:10377081,
FT ECO:0000269|PubMed:11901046, ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_008959"
FT VARIANT 1787
FT /note="S -> N (in dbSNP:rs199473316)"
FT /evidence="ECO:0000269|PubMed:10973849,
FT ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:20129283"
FT /id="VAR_009938"
FT VARIANT 1790
FT /note="D -> G (in LQT3; dbSNP:rs199473317)"
FT /evidence="ECO:0000269|PubMed:16414944,
FT ECO:0000269|PubMed:9686753"
FT /id="VAR_001580"
FT VARIANT 1792
FT /note="D -> N (in SSS1; dbSNP:rs727504495)"
FT /evidence="ECO:0000269|PubMed:22795782"
FT /id="VAR_068475"
FT VARIANT 1795
FT /note="Y -> C (in LQT3; also in a family associating LQT
FT syndrome and atrial fibrillation; slows the onset of
FT activation, but does not cause a marked negative shift in
FT the voltage dependence of inactivation or affect the
FT kinetics of the recovery from inactivation; increases the
FT expression of sustained Na(+) channel activity and promotes
FT entrance into an intermediate or slowly developing
FT inactivated state; dbSNP:rs137854614)"
FT /evidence="ECO:0000269|PubMed:11410597,
FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:18929331,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_019123"
FT VARIANT 1795
FT /note="Y -> H (in BRGDA1; accelerates the onset of
FT activation and causes a marked negative shift in the
FT voltage dependence of inactivation; does not affect the
FT kinetics of the recovery from inactivation; increases the
FT expression of sustained Na(+) channel activity and promotes
FT entrance into an intermediate or slowly developing
FT inactivated state; dbSNP:rs137854615)"
FT /evidence="ECO:0000269|PubMed:11410597,
FT ECO:0000269|PubMed:11901046"
FT /id="VAR_019124"
FT VARIANT 1795
FT /note="Y -> YD (in LQT3 and BRGDA1; 7.3-mV negative shift
FT of the steady-state inactivation curve and 8.1-mV positive
FT shift of the steady-state activation curve; may reduce
FT sodium current during the upstroke of the action
FT potential)"
FT /evidence="ECO:0000269|PubMed:10590249,
FT ECO:0000269|PubMed:11889015"
FT /id="VAR_017686"
FT VARIANT 1819
FT /note="D -> N (in LQT3; digenic; the patient also carries
FT mutation G-100 on KCNH2; dbSNP:rs137854619)"
FT /evidence="ECO:0000269|PubMed:16922724"
FT /id="VAR_036668"
FT VARIANT 1825
FT /note="L -> P (in LQT3; drug-induced LQT syndrome;
FT dbSNP:rs79299226)"
FT /id="VAR_055213"
FT VARIANT 1826
FT /note="R -> C (in ATFB10; dbSNP:rs199473635)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055214"
FT VARIANT 1826
FT /note="R -> H (in LQT3; sodium current characterized by
FT slower decay and a 2- to 3-fold increase in late sodium
FT current; dbSNP:rs137854610)"
FT /evidence="ECO:0000269|PubMed:11710892,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_017687"
FT VARIANT 1832
FT /note="Q -> E (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473320)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074473"
FT VARIANT 1836
FT /note="I -> T (in dbSNP:rs45563942)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074474"
FT VARIANT 1839
FT /note="D -> G (in LQT3; dbSNP:rs199473321)"
FT /evidence="ECO:0000269|PubMed:10627139,
FT ECO:0000269|PubMed:19716085"
FT /id="VAR_001581"
FT VARIANT 1849
FT /note="H -> R (in LQT3; decreased interaction with FGF12,
FT FGF13 and FGF14; increased voltage-gated sodium channel
FT activity; altered inactivation; dbSNP:rs794728898)"
FT /evidence="ECO:0000269|PubMed:26392562"
FT /id="VAR_076559"
FT VARIANT 1850
FT /note="C -> S (in BRGDA1; decreased I(Na) density; shift of
FT the steady-state inactivation towards negative potentials;
FT dbSNP:rs199473322)"
FT /evidence="ECO:0000269|PubMed:18252757"
FT /id="VAR_055215"
FT VARIANT 1861
FT /note="V -> I (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473636)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074475"
FT VARIANT 1872
FT /note="K -> N (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473323)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074476"
FT VARIANT 1875
FT /note="M -> T (in atrial fibrillation; pronounced
FT depolarized shift of the voltage dependence of steady-state
FT inactivation; no persistent sodium current;
FT dbSNP:rs199473324)"
FT /evidence="ECO:0000269|PubMed:18929244"
FT /id="VAR_055216"
FT VARIANT 1897
FT /note="R -> W (in LQT3; unknown pathological significance;
FT dbSNP:rs45465995)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074760"
FT VARIANT 1901
FT /note="E -> K (in dbSNP:rs199473325)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074477"
FT VARIANT 1901
FT /note="E -> Q (in LQT3; unknown pathological significance;
FT dbSNP:rs199473325)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074761"
FT VARIANT 1903
FT /note="V -> L (in BRGDA1; unknown pathological
FT significance; dbSNP:rs864622270)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074478"
FT VARIANT 1904
FT /note="S -> L (in LQT3; promotes late sodium currents by
FT increasing the propensity of the channel to reopen during
FT prolonged depolarization; dbSNP:rs150264233)"
FT /evidence="ECO:0000269|PubMed:18708744"
FT /id="VAR_055217"
FT VARIANT 1909
FT /note="Q -> R (in LQT3; dbSNP:rs199473326)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068340"
FT VARIANT 1913
FT /note="R -> H (in LQT3; unknown pathological significance;
FT dbSNP:rs199473327)"
FT /evidence="ECO:0000269|PubMed:16414944"
FT /id="VAR_074762"
FT VARIANT 1919
FT /note="R -> C (in dbSNP:rs199473328)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074479"
FT VARIANT 1924
FT /note="A -> T (in BRGDA1; significantly affect cardiac
FT sodium channel characteristics; associated with an increase
FT in inward sodium current during the action potential
FT upstroke; dbSNP:rs137854603)"
FT /evidence="ECO:0000269|PubMed:10690282,
FT ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:19251209,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_017688"
FT VARIANT 1935
FT /note="G -> S (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473637)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_055218"
FT VARIANT 1938
FT /note="E -> K (in BRGDA1; unknown pathological
FT significance; dbSNP:rs199473329)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074480"
FT VARIANT 1949
FT /note="A -> S (in LQT3; dbSNP:rs199473330)"
FT /evidence="ECO:0000269|PubMed:15840476"
FT /id="VAR_068341"
FT VARIANT 1951
FT /note="V -> L (in BRGDA1 and LQT3; also found in patients
FT with atrial fibrillation; unknown pathological
FT significance; dbSNP:rs41315493)"
FT /evidence="ECO:0000269|PubMed:11901046,
FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283"
FT /id="VAR_026386"
FT VARIANT 1951
FT /note="V -> M (in ATFB10; dbSNP:rs41315493)"
FT /evidence="ECO:0000269|PubMed:18378609"
FT /id="VAR_055219"
FT VARIANT 1958
FT /note="R -> Q (found in a patient with long QT syndrome;
FT unknown pathological significance; dbSNP:rs199473331)"
FT /evidence="ECO:0000269|PubMed:15840476,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_068342"
FT VARIANT 1962
FT /note="P -> L (in dbSNP:rs199473638)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074481"
FT VARIANT 1968
FT /note="I -> M (in dbSNP:rs199473333)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074482"
FT VARIANT 1968
FT /note="I -> S (in BRGDA1; dbSNP:rs199473639)"
FT /id="VAR_055220"
FT VARIANT 1977
FT /note="Y -> N (in LQT3; unknown pathological significance;
FT dbSNP:rs199473334)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074763"
FT VARIANT 1987
FT /note="N -> K (in ATFB10; dbSNP:rs199473335)"
FT /evidence="ECO:0000269|PubMed:18088563"
FT /id="VAR_065865"
FT VARIANT 1991
FT /note="R -> Q (in dbSNP:rs199473336)"
FT /evidence="ECO:0000269|PubMed:20129283"
FT /id="VAR_074483"
FT VARIANT 2004
FT /note="F -> L (in LQT3 and BRGDA1; also found in patients
FT with atrial fibrillation; results in channels with
FT decreased peak and persistent current amplitudes; increased
FT closed-state and slow inactivation; decelerated recovery
FT from inactivation; dbSNP:rs41311117)"
FT /evidence="ECO:0000269|PubMed:18378609,
FT ECO:0000269|PubMed:18456723, ECO:0000269|PubMed:20129283"
FT /id="VAR_055221"
FT VARIANT 2004
FT /note="F -> V (in BRGDA1 and LQT3; dbSNP:rs41311117)"
FT /evidence="ECO:0000269|PubMed:19716085,
FT ECO:0000269|PubMed:20129283"
FT /id="VAR_074484"
FT VARIANT 2006
FT /note="P -> A (found in a patient with long QT syndrome;
FT unknown pathological significance; causes an increase of
FT persistent sodium current and produces a depolarizing shift
FT in voltage dependence of inactivation; dbSNP:rs45489199)"
FT /evidence="ECO:0000269|PubMed:20129283,
FT ECO:0000269|PubMed:21109022"
FT /id="VAR_055222"
FT VARIANT 2012
FT /note="R -> C (in LQT3; unknown pathological significance;
FT dbSNP:rs199473640)"
FT /evidence="ECO:0000269|PubMed:19716085"
FT /id="VAR_074764"
FT MUTAGEN 1476
FT /note="Q->K: Induces accelerated recovery from channel fast
FT inactivation."
FT /evidence="ECO:0000269|PubMed:16054936"
FT MUTAGEN 1610
FT /note="D->A: Complete loss of channel inhibition by the
FT spider Jingzhaotoxin-I."
FT /evidence="ECO:0000269|PubMed:26721415"
FT MUTAGEN 1610
FT /note="D->R: High decrease in affinity to the sea anemone
FT toxin anthopleurin-B."
FT /evidence="ECO:0000269|PubMed:24898004"
FT MUTAGEN 1614
FT /note="K->A: 4.2-fold decrease of channel inhibition
FT potency by the spider Jingzhaotoxin-I."
FT /evidence="ECO:0000269|PubMed:26721415"
FT MUTAGEN 1802..1804
FT /note="DPE->APA: Abolishes calcium response on channel
FT inactivation."
FT /evidence="ECO:0000269|PubMed:19074138"
FT MUTAGEN 1974
FT /note="P->A: Strongly reduces interaction with NEDD4,
FT NEDD4L or WWP2."
FT /evidence="ECO:0000269|PubMed:15548568"
FT MUTAGEN 1975
FT /note="P->A: Strongly reduces interaction with NEDD4,
FT NEDD4L or WWP2."
FT /evidence="ECO:0000269|PubMed:15548568"
FT MUTAGEN 1976
FT /note="S->A: Strongly reduces interaction with NEDD4,
FT NEDD4L or WWP2."
FT /evidence="ECO:0000269|PubMed:15548568"
FT MUTAGEN 1977
FT /note="Y->A: Strongly reduces interaction with NEDD4,
FT NEDD4L or WWP2."
FT /evidence="ECO:0000269|PubMed:15217910,
FT ECO:0000269|PubMed:15548568"
FT MUTAGEN 1978
FT /note="D->A: No effect on interaction with NEDD4, NEDD4L or
FT WWP2."
FT /evidence="ECO:0000269|PubMed:15548568"
FT MUTAGEN 1979
FT /note="S->A: No effect on interaction with NEDD4, NEDD4L or
FT WWP2."
FT /evidence="ECO:0000269|PubMed:15548568"
FT MUTAGEN 1980
FT /note="V->A: No effect on interaction with NEDD4, NEDD4L or
FT WWP2."
FT /evidence="ECO:0000269|PubMed:15217910,
FT ECO:0000269|PubMed:15548568"
FT MUTAGEN 1980
FT /note="V->D,R: Strongly reduces interaction with NEDD4L."
FT /evidence="ECO:0000269|PubMed:15217910,
FT ECO:0000269|PubMed:15548568"
FT CONFLICT 91
FT /note="K -> R (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="I -> V (in Ref. 1; AAA58644)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="Y -> H (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="G -> A (in Ref. 1; AAA58644)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="F -> S (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="D -> G (in Ref. 5; BAD12084/BAD12085 and 6;
FT ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="V -> L (in Ref. 5; BAD12084/BAD12085, 6; ABR15763/
FT ABR15764 and 9; AAI44622/AAI40814)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="S -> P (in Ref. 5; BAD12084/BAD12085, 6; ABR15763/
FT ABR15764 and 9; AAI44622/AAI40814)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="C -> R (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="T -> I (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="S -> N (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 608
FT /note="D -> N (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="L -> I (in Ref. 4; AAO91669)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="F -> V (in Ref. 5; BAD12084/BAD12085)"
FT /evidence="ECO:0000305"
FT CONFLICT 918
FT /note="V -> G (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 987
FT /note="Q -> H (in Ref. 1; AAA58644, 5; BAD12084/BAD12085
FT and 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 1085
FT /note="G -> W (in Ref. 1; AAA58644 and 5; BAD12084)"
FT /evidence="ECO:0000305"
FT CONFLICT 1087
FT /note="E -> R (in Ref. 1; AAA58644 and 5; BAD12084)"
FT /evidence="ECO:0000305"
FT CONFLICT 1088
FT /note="A -> G (in Ref. 1; AAA58644 and 5; BAD12084)"
FT /evidence="ECO:0000305"
FT CONFLICT 1342
FT /note="L -> H (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 1479
FT /note="K -> T (in Ref. 5; BAD12084/BAD12085)"
FT /evidence="ECO:0000305"
FT CONFLICT 1480..1481
FT /note="LG -> IR (in Ref. 7; ABQ01244)"
FT /evidence="ECO:0000305"
FT CONFLICT 1616
FT /note="F -> S (in Ref. 10; BAD92103)"
FT /evidence="ECO:0000305"
FT CONFLICT 1657
FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT CONFLICT 1850
FT /note="C -> R (in Ref. 6; ABR15763/ABR15764)"
FT /evidence="ECO:0000305"
FT HELIX 121..128
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 131..148
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 157..178
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 185..191
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 193..207
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 218..223
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 224..227
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:7DTC"
FT HELIX 236..250
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 253..272
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 273..276
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 304..307
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:7DTC"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 358..369
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 370..373
FT /evidence="ECO:0007829|PDB:7DTC"
FT HELIX 374..385
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 390..399
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 401..428
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 700..714
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 717..720
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 721..734
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 738..740
FT /evidence="ECO:0007829|PDB:7DTC"
FT HELIX 745..770
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 773..776
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 780..782
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 783..797
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 806..812
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 813..819
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 825..835
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 836..838
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 842..861
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 862..864
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 865..868
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 872..874
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 884..896
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 900..910
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 912..942
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1191..1203
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1205..1220
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1221..1224
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1230..1232
FT /evidence="ECO:0007829|PDB:7DTC"
FT HELIX 1233..1267
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1269..1271
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1272..1290
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1299..1303
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1304..1315
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1318..1329
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1332..1356
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1361..1364
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1366..1368
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1375..1377
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1381..1386
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1394..1397
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1402..1404
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1405..1416
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1422..1429
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1433..1436
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1440..1443
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1444..1446
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1447..1477
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1480..1482
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1491..1500
FT /evidence="ECO:0007829|PDB:4DJC"
FT STRAND 1501..1504
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1516..1526
FT /evidence="ECO:0007829|PDB:5DBR"
FT HELIX 1528..1546
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1554..1581
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1583..1586
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1589..1591
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1592..1608
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1609..1614
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1621..1626
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1627..1635
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1636..1639
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1641..1651
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1654..1678
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1679..1681
FT /evidence="ECO:0007829|PDB:7DTC"
FT STRAND 1690..1696
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1697..1708
FT /evidence="ECO:0007829|PDB:6LQA"
FT TURN 1709..1713
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1714..1720
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1724..1727
FT /evidence="ECO:0007829|PDB:6LQA"
FT STRAND 1735..1737
FT /evidence="ECO:0007829|PDB:7DTC"
FT HELIX 1745..1780
FT /evidence="ECO:0007829|PDB:6LQA"
FT HELIX 1788..1801
FT /evidence="ECO:0007829|PDB:4DCK"
FT STRAND 1807..1810
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1811..1813
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1814..1820
FT /evidence="ECO:0007829|PDB:4DCK"
FT TURN 1823..1825
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1832..1837
FT /evidence="ECO:0007829|PDB:4DCK"
FT STRAND 1841..1843
FT /evidence="ECO:0007829|PDB:4DCK"
FT TURN 1844..1846
FT /evidence="ECO:0007829|PDB:4DCK"
FT STRAND 1847..1849
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1850..1862
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1866..1882
FT /evidence="ECO:0007829|PDB:4DCK"
FT HELIX 1886..1888
FT /evidence="ECO:0007829|PDB:4DCK"
FT STRAND 1891..1894
FT /evidence="ECO:0007829|PDB:4OVN"
FT HELIX 1896..1926
FT /evidence="ECO:0007829|PDB:4DCK"
SQ SEQUENCE 2016 AA; 226940 MW; 841E3A365931190B CRC64;
MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSTTLQ ESREGLPEEE APRPQLDLQA
SKKLPDLYGN PPQELIGEPL EDLDPFYSTQ KTFIVLNKGK TIFRFSATNA LYVLSPFHPI
RRAAVKILVH SLFNMLIMCT ILTNCVFMAQ HDPPPWTKYV EYTFTAIYTF ESLVKILARG
FCLHAFTFLR DPWNWLDFSV IIMAYTTEFV DLGNVSALRT FRVLRALKTI SVISGLKTIV
GALIQSVKKL ADVMVLTVFC LSVFALIGLQ LFMGNLRHKC VRNFTALNGT NGSVEADGLV
WESLDLYLSD PENYLLKNGT SDVLLCGNSS DAGTCPEGYR CLKAGENPDH GYTSFDSFAW
AFLALFRLMT QDCWERLYQQ TLRSAGKIYM IFFMLVIFLG SFYLVNLILA VVAMAYEEQN
QATIAETEEK EKRFQEAMEM LKKEHEALTI RGVDTVSRSS LEMSPLAPVN SHERRSKRRK
RMSSGTEECG EDRLPKSDSE DGPRAMNHLS LTRGLSRTSM KPRSSRGSIF TFRRRDLGSE
ADFADDENST AGESESHHTS LLVPWPLRRT SAQGQPSPGT SAPGHALHGK KNSTVDCNGV
VSLLGAGDPE ATSPGSHLLR PVMLEHPPDT TTPSEEPGGP QMLTSQAPCV DGFEEPGARQ
RALSAVSVLT SALEELEESR HKCPPCWNRL AQRYLIWECC PLWMSIKQGV KLVVMDPFTD
LTITMCIVLN TLFMALEHYN MTSEFEEMLQ VGNLVFTGIF TAEMTFKIIA LDPYYYFQQG
WNIFDSIIVI LSLMELGLSR MSNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG
NLTLVLAIIV FIFAVVGMQL FGKNYSELRD SDSGLLPRWH MMDFFHAFLI IFRILCGEWI
ETMWDCMEVS GQSLCLLVFL LVMVIGNLVV LNLFLALLLS SFSADNLTAP DEDREMNNLQ
LALARIQRGL RFVKRTTWDF CCGLLRQRPQ KPAALAAQGQ LPSCIATPYS PPPPETEKVP
PTRKETRFEE GEQPGQGTPG DPEPVCVPIA VAESDTDDQE EDEENSLGTE EESSKQQESQ
PVSGGPEAPP DSRTWSQVSA TASSEAEASA SQADWRQQWK AEPQAPGCGE TPEDSCSEGS
TADMTNTAEL LEQIPDLGQD VKDPEDCFTE GCVRRCPCCA VDTTQAPGKV WWRLRKTCYH
IVEHSWFETF IIFMILLSSG ALAFEDIYLE ERKTIKVLLE YADKMFTYVF VLEMLLKWVA
YGFKKYFTNA WCWLDFLIVD VSLVSLVANT LGFAEMGPIK SLRTLRALRP LRALSRFEGM
RVVVNALVGA IPSIMNVLLV CLIFWLIFSI MGVNLFAGKF GRCINQTEGD LPLNYTIVNN
KSQCESLNLT GELYWTKVKV NFDNVGAGYL ALLQVATFKG WMDIMYAAVD SRGYEEQPQW
EYNLYMYIYF VIFIIFGSFF TLNLFIGVII DNFNQQKKKL GGQDIFMTEE QKKYYNAMKK
LGSKKPQKPI PRPLNKYQGF IFDIVTKQAF DVTIMFLICL NMVTMMVETD DQSPEKINIL
AKINLLFVAI FTGECIVKLA ALRHYYFTNS WNIFDFVVVI LSIVGTVLSD IIQKYFFSPT
LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGMANFA
YVKWEAGIDD MFNFQTFANS MLCLFQITTS AGWDGLLSPI LNTGPPYCDP TLPNSNGSRG
DCGSPAVGIL FFTTYIIISF LIVVNMYIAI ILENFSVATE ESTEPLSEDD FDMFYEIWEK
FDPEATQFIE YSVLSDFADA LSEPLRIAKP NQISLINMDL PMVSGDRIHC MDILFAFTKR
VLGESGEMDA LKIQMEEKFM AANPSKISYE PITTTLRRKH EEVSAMVIQR AFRRHLLQRS
LKHASFLFRQ QAGSGLSEED APEREGLIAY VMSENFSRPL GPPSSSSISS TSFPPSYDSV
TRATSDNLQV RGSDYSHSED LADFPPSPDR DRESIV
