| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ2 | A306T | Epilepsy, benign neonatal | High | 9 | 9425895, 19453707, 26138355 |
| KCNQ2 | A306V | Sudden unexpected death in epilepsy | High | 9 | 26704558 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in KCNQ1.
| KCNQ1 | TTIGYGDKVPQTWVGKTIASCFSVFAISFF>A<LPAGILGSGFALKVQQKQRQKHFNRQIPA- | 370 |
| KCNQ2 | TTIGYGDKYPQTWNGRLLAATFTLIGVSFF>A<LPAGILGSGFALKVQEQHRQKHFEKRRNP- | 335 |
| KCNQ3 | ATIGYGDKTPKTWEGRLIAATFSLIGVSFF>A<LPAGILGSGLALKVQEQHRQKHFEKRRKP- | 374 |
| KCNQ4 | TTIGYGDKTPHTWLGRVLAAGFALLGISFF>A<LPAGILGSGFALKVQEQHRQKHFEKRRMP- | 341 |
| KCNQ5 | TTIGYGDKTPLTWLGRLLSAGFALLGISFF>A<LPAGILGSGFALKVQEQHRQKHFEKRRNP- | 369 |
| KCNA1 | TTVGYGDMYPVTIGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETEGEEQAQLLH-- | 429 |
| KCNA10 | TTVGYGDMCPTTPGGKIVGTLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETENEEKQNIPGEI | 480 |
| KCNA2 | TTVGYGDMVPTTIGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETEGEEQAQYLQ-- | 431 |
| KCNA3 | TTVGYGDMHPVTIGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETEGEEQSQYMH-- | 501 |
| KCNA4 | TTVGYGDMKPITVGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETENEEQTQLTQ-- | 581 |
| KCNA5 | TTVGYGDMRPITVGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETDHEEPAVLKEE- | 538 |
| KCNA6 | TTVGYGDMYPMTVGGKIVGSLCAIAGVLTI>A<LPVPVIVSNFNYFYHRETEQEEQGQYTHV- | 480 |
| KCNA7 | TTVGYGDMAPVTVGGKIVGSLCAIAGVLTI>S<LPVPVIVSNFSYFYHRETEGEEAGMFSHV- | 416 |
| KCNB1 | TTVGYGDIYPKTLLGKIVGGLCCIAGVLVI>A<LPIPIIVNNFSEFYKEQKRQEKAIKRREA- | 435 |
| KCNB2 | TTVGYGDIYPKTLLGKIVGGLCCIAGVLVI>A<LPIPIIVNNFSEFYKEQKRQEKAIKRREA- | 439 |
| KCNC1 | TTLGYGDMYPQTWSGMLVGALCALAGVLTI>A<MPVPVIVNNFGMYYSLAMAKQKLPKKKKK- | 458 |
| KCNC2 | TTLGYGDMYPQTWSGMLVGALCALAGVLTI>A<MPVPVIVNNFGMYYSLAMAKQKLPRKRKK- | 495 |
| KCNC3 | TTLGYGDMYPKTWSGMLVGALCALAGVLTI>A<MPVPVIVNNFGMYYSLAMAKQKLPKKKNK- | 561 |
| KCNC4 | TTLGYGDMYPKTWSGMLVGALCALAGVLTI>A<MPVPVIVNNFGMYYSLAMAKQKLPKKRKK- | 494 |
| KCND1 | TTLGYGDMVPSTIAGKIFGSICSLSGVLVI>A<LPVPVIVSNFSRIYHQNQRADKRRAQQKV- | 430 |
| KCND2 | TTLGYGDMVPKTIAGKIFGSICSLSGVLVI>A<LPVPVIVSNFSRIYHQNQRADKRRAQKKA- | 428 |
| KCND3 | TTLGYGDMVPKTIAGKIFGSICSLSGVLVI>A<LPVPVIVSNFSRIYHQNQRADKRRAQKKA- | 425 |
| KCNF1 | TTVGYGDIYPKTTLGKLNAAISFLCGVIAI>A<LPIHPIINNFVRYYNKQRVLETAAKHELE- | 428 |
| KCNG1 | TTVGYGDMVPRSTPGQVVALSSILSGILLM>A<FPVTSIFHTFSRSYLELKQEQERVMFRRA- | 482 |
| KCNG2 | TTVGYGDMVPRSLPGQVVALSSILSGILLM>A<FPVTSIFHTFSRSYSELKEQQQRAASPEP- | 427 |
| KCNG3 | TTVGYGDMYPITVPGRILGGVCVVSGIVLL>A<LPITFIYHSFVQCYHELKFRSARYSR---- | 428 |
| KCNG4 | TTVGYGDMVPRSVPGQMVALSSILSGILIM>A<FPATSIFHTFSHSYLELKKEQEQLQARLR- | 476 |
| KCNS1 | TTVGYGDVVPVTVAGKLAASGCILGGILVV>A<LPITIIFNKFSHFYRRQKALEAAVRNSNH- | 479 |
| KCNS2 | TTVGYGDVVPGTTAGKLTASACILAGILVV>V<LPITLIFNKFSHFYRRQKQLESAMRSCDF- | 432 |
| KCNS3 | TTVGYGDTHPVTLAGKLIASTCIICGILVV>A<LPITIIFNKFSKYYQKQKDIDVDQCSEDA- | 428 |
| KCNV1 | TTVGYGDIRPDTTTGKIVAFMCILSGILVL>A<LPIAIINDRFSACYFTLKLKEAAVRQREA- | 450 |
| KCNV2 | STVGYGDMYPETHLGRFFAFLCIAFGIILN>G<MPISILYNKFSDYYSKLKAYEYTTIRRER- | 515 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.A341E | c.1022C>A | Inherited Arrhythmia | LQTS | rs12720459 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244 | ||
| Inherited Arrhythmia | LQTS | C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence. Circulation. 1999 99(11):1464-70. 10086971 | |||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death. Clin Genet. 2003 63(4):273-82. 12702160 | |||
| Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | |||
| Inherited Arrhythmia | LQTS | The common long-QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation. 2007 116(21):2366-75. 17984373 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| Inherited Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med. 2009 1(2):2ra6. 20368164 | |||
| Inherited Arrhythmia | LQTS | Functional effects of mutations in KvLQT1 that cause long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(6):817-26. 10376919 | |||
| Inherited Arrhythmia | LQTS | Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695 | |||
| Inherited Arrhythmia | LQTS | Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Circ Cardiovasc Genet. 2012 5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. 22949429 | |||
| p.A341G | c.1022C>G | Inherited Arrhythmia | LQTS | rs12720459 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | ||
| p.A341V | c.1022C>T | Inherited Arrhythmia | LQTS | rs12720459 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244 | ||
| Inherited Arrhythmia | LQTS | Evidence of a long QT founder gene with varying phenotypic expression in South African families. J Med Genet. 1996 33(7):567-73. 8818942 | |||
| Inherited Arrhythmia | LQTS | KVLQT1 mutations in three families with familial or sporadic long QT syndrome. Hum Mol Genet. 1996 5(9):1319-24. 8872472 | |||
| Inherited Arrhythmia | LQTS | KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136 | |||
| Inherited Arrhythmia | LQTS | New mutations in the KVLQT1 potassium channel that cause long-QT syndrome. Circulation. 1998 97(13):1264-9. 9570196 | |||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | DHPLC analysis of potassium ion channel genes in congenital long QT syndrome. Hum Mutat. 2002 20(5):382-91. 12402336 | |||
| Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | |||
| Inherited Arrhythmia | LQTS | Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 15(2):190-9. 15028050 | |||
| Inherited Arrhythmia | LQTS | Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636 | |||
| Inherited Arrhythmia | LQTS | Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476 | |||
| Inherited Arrhythmia | LQTS | Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms. J Hum Genet. 2005 50(9):490-6. 16155735 | |||
| Inherited Arrhythmia | LQTS | Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| Inherited Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | Identification and functional characterization of KCNQ1 mutations around the exon 7-intron 7 junction affecting the splicing process. Biochim Biophys Acta. 2011 1812(11):1452-9. 21810471 | |||
| Inherited Arrhythmia | LQTS | Functional effects of mutations in KvLQT1 that cause long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(6):817-26. 10376919 | |||
| Inherited Arrhythmia | LQTS | Partial restoration of the long QT syndrome associated KCNQ1 A341V mutant by the KCNE1 β-subunit. Biochim Biophys Acta. 2011 1810(12):1285-93. 21854832 | |||
| Inherited Arrhythmia | LQTS | Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan. J Am Coll Cardiol. 2004 44(1):117-25. 15234419 | |||
| Inherited Arrhythmia | LQTS | Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population. Circulation. 2005 112(17):2602-10. 16246960 | |||
| Inherited Arrhythmia | LQTS | Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome. J Am Coll Cardiol. 2008 51(9):920-9. 18308161 | |||
| Inherited Arrhythmia | LQTS | Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695 | |||
| Inherited Arrhythmia | LQTS | Dominant-negative control of cAMP-dependent IKs upregulation in human long-QT syndrome type 1. Circ Res. 2012 110(2):211-9. 22095730 | |||
| Inherited Arrhythmia | LQTS | Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Circ Cardiovasc Genet. 2012 5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. 22949429 | |||
| Inherited Arrhythmia | LQTS | The common long-QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation. 2007 116(21):2366-75. 17984373 | |||
| Inherited Arrhythmia | LQTS | Multiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1. PLoS One. 2014 9(4):e93808. doi: 10.1371/journal.pone.0093808. eC 24705789 | |||
| Inherited Arrhythmia | LQTS | Cellular mechanisms underlying the increased disease severity seen for patients with long QT syndrome caused by compound mutations in KCNQ1. Biochem J. 2014 462(1):133-42. doi: 10.1042/BJ20140425. 24912595 | |||
| Inherited Arrhythmia | LQTS | Autonomic control of heart rate and QT interval variability influences arrhythmic risk in long QT syndrome type 1. J Am Coll Cardiol. 2015 65(4):367-74. doi: 10.1016/j.jacc.2014.11.015. 25634836 | |||