Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
---|---|---|---|---|---|
KCNQ4 | Y286C | Hearing loss | High | 9 | 26969326 |
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 | -----ESGRVEFGSYADALWWGVVTVTTIG>Y<GDKVPQTWVGKTIASCFSVFAISFFALPAG | 345 |
KCNQ2 | --------NDHFDTYADALWWGLITLTTIG>Y<GDKYPQTWNGRLLAATFTLIGVSFFALPAG | 310 |
KCNQ3 | VDAQGEEMKEEFETYADALWWGLITLATIG>Y<GDKTPKTWEGRLIAATFSLIGVSFFALPAG | 349 |
KCNQ4 | --------NSDFSSYADSLWWGTITLTTIG>Y<GDKTPHTWLGRVLAAGFALLGISFFALPAG | 316 |
KCNQ5 | --------NKEFSTYADALWWGTITLTTIG>Y<GDKTPLTWLGRLLSAGFALLGISFFALPAG | 344 |
KCNA1 | -------AESHFSSIPDAFWWAVVSMTTVG>Y<GDMYPVTIGGKIVGSLCAIAGVLTIALPVP | 405 |
KCNA10 | -------PESHFSSIPDGFWWAVVTMTTVG>Y<GDMCPTTPGGKIVGTLCAIAGVLTIALPVP | 454 |
KCNA2 | -------RESQFPSIPDAFWWAVVSMTTVG>Y<GDMVPTTIGGKIVGSLCAIAGVLTIALPVP | 407 |
KCNA3 | -------PTSGFSSIPDAFWWAVVTMTTVG>Y<GDMHPVTIGGKIVGSLCAIAGVLTIALPVP | 477 |
KCNA4 | -------PTTHFQSIPDAFWWAVVTMTTVG>Y<GDMKPITVGGKIVGSLCAIAGVLTIALPVP | 557 |
KCNA5 | -------QGTHFSSIPDAFWWAVVTMTTVG>Y<GDMRPITVGGKIVGSLCAIAGVLTIALPVP | 513 |
KCNA6 | -------DDSLFPSIPDAFWWAVVTMTTVG>Y<GDMYPMTVGGKIVGSLCAIAGVLTIALPVP | 455 |
KCNA7 | -------VDSHFTSIPESFWWAVVTMTTVG>Y<GDMAPVTVGGKIVGSLCAIAGVLTISLPVP | 391 |
KCNB1 | -------DDTKFKSIPASFWWATITMTTVG>Y<GDIYPKTLLGKIVGGLCCIAGVLVIALPIP | 410 |
KCNB2 | -------DATKFTSIPASFWWATITMTTVG>Y<GDIYPKTLLGKIVGGLCCIAGVLVIALPIP | 414 |
KCNC1 | PNDPSASEHTHFKNIPIGFWWAVVTMTTLG>Y<GDMYPQTWSGMLVGALCALAGVLTIAMPVP | 433 |
KCNC2 | PNDPSASEHTQFKNIPIGFWWAVVTMTTLG>Y<GDMYPQTWSGMLVGALCALAGVLTIAMPVP | 470 |
KCNC3 | PDDILGSNHTYFKNIPIGFWWAVVTMTTLG>Y<GDMYPKTWSGMLVGALCALAGVLTIAMPVP | 536 |
KCNC4 | PSDPRGNDHTDFKNIPIGFWWAVVTMTTLG>Y<GDMYPKTWSGMLVGALCALAGVLTIAMPVP | 469 |
KCND1 | -------NKTNFTSIPAAFWYTIVTMTTLG>Y<GDMVPSTIAGKIFGSICSLSGVLVIALPVP | 405 |
KCND2 | -------SASKFTSIPAAFWYTIVTMTTLG>Y<GDMVPKTIAGKIFGSICSLSGVLVIALPVP | 403 |
KCND3 | -------SASKFTSIPASFWYTIVTMTTLG>Y<GDMVPKTIAGKIFGSICSLSGVLVIALPVP | 400 |
KCNF1 | -------PETLFKSIPQSFWWAIITMTTVG>Y<GDIYPKTTLGKLNAAISFLCGVIAIALPIH | 403 |
KCNG1 | ---A---DSPEFTSIPACYWWAVITMTTVG>Y<GDMVPRSTPGQVVALSSILSGILLMAFPVT | 457 |
KCNG2 | ---G---ARRDFSSVPASYWWAVISMTTVG>Y<GDMVPRSLPGQVVALSSILSGILLMAFPVT | 402 |
KCNG3 | ---DLETSNKDFTSIPAACWWVIISMTTVG>Y<GDMYPITVPGRILGGVCVVSGIVLLALPIT | 406 |
KCNG4 | ---G---RVLEFTSIPASYWWAIISMTTVG>Y<GDMVPRSVPGQMVALSSILSGILIMAFPAT | 451 |
KCNS1 | --------DVGFNTIPACWWWGTVSMTTVG>Y<GDVVPVTVAGKLAASGCILGGILVVALPIT | 454 |
KCNS2 | --------NEGLATIPACWWWATVSMTTVG>Y<GDVVPGTTAGKLTASACILAGILVVVLPIT | 407 |
KCNS3 | -------HTSSLTSIPICWWWATISMTTVG>Y<GDTHPVTLAGKLIASTCIICGILVVALPIT | 403 |
KCNV1 | -------PDTTFTSVPCAWWWATTSMTTVG>Y<GDIRPDTTTGKIVAFMCILSGILVLALPIA | 425 |
KCNV2 | -------PSTNFTTIPHSWWWAAVSISTVG>Y<GDMYPETHLGRFFAFLCIAFGIILNGMPIS | 490 |
cons | > < |
Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
---|---|---|---|---|---|
p.Y315C | c.944A>G | Inherited Arrhythmia | LQTS | rs74462309 | SIFT: deleterious Polyphen: probably damaging |
Reports | 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 | Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000 11(6):691-6. 10868744 | |||
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 | Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697 | |||
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 | Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 82(3):182-8. 14760488 | |||
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 | 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 | Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999 99(4):529-33. 9927399 | |||
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 | Mechanisms of I(Ks) suppression in LQT1 mutants. Am J Physiol Heart Circ Physiol. 2000 279(6):H3003-11. 11087258 | |||
p.Y315F | c.944A>T | Inherited Arrhythmia | LQTS | rs74462309 | SIFT: deleterious Polyphen: possibly damaging |
Reports | 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 | |||
Unknown | Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510 | ||||
p.Y315S | c.944A>C | Inherited Arrhythmia | LQTS | rs74462309 | SIFT: deleterious Polyphen: probably damaging |
Reports | 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 | 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 | Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest. 2008 118(6):2246-59. 18464931 | |||
Inherited Arrhythmia | LQTS | Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines. Am J Physiol Heart Circ Physiol. 2010 299(5):H1525-34. 20833965 | |||
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 | 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 | |||
p.Y315N | c.943T>A | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
Reports | Inherited Arrhythmia | LQTS | Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol. 2012 60(24):2515-24. doi: 10.1016/j.jacc.2012.08.1009. 23158531 | ||
p.Y315H | c.943T>C | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
Reports | Inherited Arrhythmia | LQTS | Genetic analysis, in silico prediction, and family segregation in long QT syndrome. Eur J Hum Genet. 2015 23(1):79-85. doi: 10.1038/ejhg.2014.54. 24667783 |