| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ4 | G285S | Deafness, autosomal dominant 2 | High | 9 | 10025409, 23750663, 25116015 |
| KCNQ4 | G285C | Deafness, autosomal dominant 2 | High | 9 | 10369879, 20832469, 20966080, 23750663 |
| KCNV2 | G459D | Cone dystrophy with supernormal rod ERG | High | 9 | 16909397, 23115240 |
| KCNB1 | G379R | Epileptic encephalopathy | High | 9 | 25164438, 25164438 |
| KCNQ2 | G279C | Epileptic encephalopathy, type 7 | High | 9 | 25959266 |
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 | N-----ESGRVEFGSYADALWWGVVTVTTI>G<YGDKVPQTWVGKTIASCFSVFAISFFALPA | 344 |
| KCNQ2 | ---------NDHFDTYADALWWGLITLTTI>G<YGDKYPQTWNGRLLAATFTLIGVSFFALPA | 309 |
| KCNQ3 | EVDAQGEEMKEEFETYADALWWGLITLATI>G<YGDKTPKTWEGRLIAATFSLIGVSFFALPA | 348 |
| KCNQ4 | ---------NSDFSSYADSLWWGTITLTTI>G<YGDKTPHTWLGRVLAAGFALLGISFFALPA | 315 |
| KCNQ5 | ---------NKEFSTYADALWWGTITLTTI>G<YGDKTPLTWLGRLLSAGFALLGISFFALPA | 343 |
| KCNA1 | --------AESHFSSIPDAFWWAVVSMTTV>G<YGDMYPVTIGGKIVGSLCAIAGVLTIALPV | 404 |
| KCNA10 | --------PESHFSSIPDGFWWAVVTMTTV>G<YGDMCPTTPGGKIVGTLCAIAGVLTIALPV | 453 |
| KCNA2 | --------RESQFPSIPDAFWWAVVSMTTV>G<YGDMVPTTIGGKIVGSLCAIAGVLTIALPV | 406 |
| KCNA3 | --------PTSGFSSIPDAFWWAVVTMTTV>G<YGDMHPVTIGGKIVGSLCAIAGVLTIALPV | 476 |
| KCNA4 | --------PTTHFQSIPDAFWWAVVTMTTV>G<YGDMKPITVGGKIVGSLCAIAGVLTIALPV | 556 |
| KCNA5 | --------QGTHFSSIPDAFWWAVVTMTTV>G<YGDMRPITVGGKIVGSLCAIAGVLTIALPV | 512 |
| KCNA6 | --------DDSLFPSIPDAFWWAVVTMTTV>G<YGDMYPMTVGGKIVGSLCAIAGVLTIALPV | 454 |
| KCNA7 | --------VDSHFTSIPESFWWAVVTMTTV>G<YGDMAPVTVGGKIVGSLCAIAGVLTISLPV | 390 |
| KCNB1 | --------DDTKFKSIPASFWWATITMTTV>G<YGDIYPKTLLGKIVGGLCCIAGVLVIALPI | 409 |
| KCNB2 | --------DATKFTSIPASFWWATITMTTV>G<YGDIYPKTLLGKIVGGLCCIAGVLVIALPI | 413 |
| KCNC1 | QPNDPSASEHTHFKNIPIGFWWAVVTMTTL>G<YGDMYPQTWSGMLVGALCALAGVLTIAMPV | 432 |
| KCNC2 | QPNDPSASEHTQFKNIPIGFWWAVVTMTTL>G<YGDMYPQTWSGMLVGALCALAGVLTIAMPV | 469 |
| KCNC3 | DPDDILGSNHTYFKNIPIGFWWAVVTMTTL>G<YGDMYPKTWSGMLVGALCALAGVLTIAMPV | 535 |
| KCNC4 | RPSDPRGNDHTDFKNIPIGFWWAVVTMTTL>G<YGDMYPKTWSGMLVGALCALAGVLTIAMPV | 468 |
| KCND1 | --------NKTNFTSIPAAFWYTIVTMTTL>G<YGDMVPSTIAGKIFGSICSLSGVLVIALPV | 404 |
| KCND2 | --------SASKFTSIPAAFWYTIVTMTTL>G<YGDMVPKTIAGKIFGSICSLSGVLVIALPV | 402 |
| KCND3 | --------SASKFTSIPASFWYTIVTMTTL>G<YGDMVPKTIAGKIFGSICSLSGVLVIALPV | 399 |
| KCNF1 | --------PETLFKSIPQSFWWAIITMTTV>G<YGDIYPKTTLGKLNAAISFLCGVIAIALPI | 402 |
| KCNG1 | ----A---DSPEFTSIPACYWWAVITMTTV>G<YGDMVPRSTPGQVVALSSILSGILLMAFPV | 456 |
| KCNG2 | ----G---ARRDFSSVPASYWWAVISMTTV>G<YGDMVPRSLPGQVVALSSILSGILLMAFPV | 401 |
| KCNG3 | ----DLETSNKDFTSIPAACWWVIISMTTV>G<YGDMYPITVPGRILGGVCVVSGIVLLALPI | 405 |
| KCNG4 | ----G---RVLEFTSIPASYWWAIISMTTV>G<YGDMVPRSVPGQMVALSSILSGILIMAFPA | 450 |
| KCNS1 | ---------DVGFNTIPACWWWGTVSMTTV>G<YGDVVPVTVAGKLAASGCILGGILVVALPI | 453 |
| KCNS2 | ---------NEGLATIPACWWWATVSMTTV>G<YGDVVPGTTAGKLTASACILAGILVVVLPI | 406 |
| KCNS3 | --------HTSSLTSIPICWWWATISMTTV>G<YGDTHPVTLAGKLIASTCIICGILVVALPI | 402 |
| KCNV1 | --------PDTTFTSVPCAWWWATTSMTTV>G<YGDIRPDTTTGKIVAFMCILSGILVLALPI | 424 |
| KCNV2 | --------PSTNFTTIPHSWWWAAVSISTV>G<YGDMYPETHLGRFFAFLCIAFGIILNGMPI | 489 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.G314A | c.941G>C | Inherited Arrhythmia | LQTS | rs199472748 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | 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 | |||
| p.G314C | c.940G>T | Inherited Arrhythmia | LQTS | rs120074184 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | 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.G314D | c.941G>A | Inherited Arrhythmia | LQTS | rs199472748 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet. 2003 40(2):141-5. 12566525 | ||
| Inherited Arrhythmia | LQTS | Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation. 2004 110(15):2119-24. 15466642 | |||
| 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 | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| 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.G314R | c.940G>C | Inherited Arrhythmia | LQTS | rs120074184 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | ||
| p.G314S | c.940G>A | Inherited Arrhythmia | LQTS | rs120074184 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998 51(1):86-97. 9693036 | |||
| Inherited Arrhythmia | LQTS | Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome. Hum Genet. 1998 103(3):290-4. 9799083 | |||
| Inherited Arrhythmia | LQTS | Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144 | |||
| Inherited Arrhythmia | LQTS | The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet. 2003 40(2):141-5. 12566525 | |||
| 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 | [Relationship between congenital long QT syndrome and Brugada syndrome gene mutation]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 27(3):289-94. 16038262 | |||
| 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 | The G314S KCNQ1 mutation exerts a dominant-negative effect on expression of KCNQ1 channels in oocytes. Biochem Biophys Res Commun. 2009 383(2):206-9. 19348785 | |||
| 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 | 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 | 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 | |||
| Inherited Arrhythmia | LQTS | Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 16(17):5472-9. 9312006 | |||