Paralogue Annotation for KCNQ1 residue 315

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 315
Reference Amino Acid: Y - Tyrosine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 315

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ4Y286CHearing lossHigh9 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<GDKVPQTWVGKTIASCFSVFAISFFALPAG345
KCNQ2--------NDHFDTYADALWWGLITLTTIG>Y<GDKYPQTWNGRLLAATFTLIGVSFFALPAG310
KCNQ3VDAQGEEMKEEFETYADALWWGLITLATIG>Y<GDKTPKTWEGRLIAATFSLIGVSFFALPAG349
KCNQ4--------NSDFSSYADSLWWGTITLTTIG>Y<GDKTPHTWLGRVLAAGFALLGISFFALPAG316
KCNQ5--------NKEFSTYADALWWGTITLTTIG>Y<GDKTPLTWLGRLLSAGFALLGISFFALPAG344
KCNA1-------AESHFSSIPDAFWWAVVSMTTVG>Y<GDMYPVTIGGKIVGSLCAIAGVLTIALPVP405
KCNA10-------PESHFSSIPDGFWWAVVTMTTVG>Y<GDMCPTTPGGKIVGTLCAIAGVLTIALPVP454
KCNA2-------RESQFPSIPDAFWWAVVSMTTVG>Y<GDMVPTTIGGKIVGSLCAIAGVLTIALPVP407
KCNA3-------PTSGFSSIPDAFWWAVVTMTTVG>Y<GDMHPVTIGGKIVGSLCAIAGVLTIALPVP477
KCNA4-------PTTHFQSIPDAFWWAVVTMTTVG>Y<GDMKPITVGGKIVGSLCAIAGVLTIALPVP557
KCNA5-------QGTHFSSIPDAFWWAVVTMTTVG>Y<GDMRPITVGGKIVGSLCAIAGVLTIALPVP513
KCNA6-------DDSLFPSIPDAFWWAVVTMTTVG>Y<GDMYPMTVGGKIVGSLCAIAGVLTIALPVP455
KCNA7-------VDSHFTSIPESFWWAVVTMTTVG>Y<GDMAPVTVGGKIVGSLCAIAGVLTISLPVP391
KCNB1-------DDTKFKSIPASFWWATITMTTVG>Y<GDIYPKTLLGKIVGGLCCIAGVLVIALPIP410
KCNB2-------DATKFTSIPASFWWATITMTTVG>Y<GDIYPKTLLGKIVGGLCCIAGVLVIALPIP414
KCNC1PNDPSASEHTHFKNIPIGFWWAVVTMTTLG>Y<GDMYPQTWSGMLVGALCALAGVLTIAMPVP433
KCNC2PNDPSASEHTQFKNIPIGFWWAVVTMTTLG>Y<GDMYPQTWSGMLVGALCALAGVLTIAMPVP470
KCNC3PDDILGSNHTYFKNIPIGFWWAVVTMTTLG>Y<GDMYPKTWSGMLVGALCALAGVLTIAMPVP536
KCNC4PSDPRGNDHTDFKNIPIGFWWAVVTMTTLG>Y<GDMYPKTWSGMLVGALCALAGVLTIAMPVP469
KCND1-------NKTNFTSIPAAFWYTIVTMTTLG>Y<GDMVPSTIAGKIFGSICSLSGVLVIALPVP405
KCND2-------SASKFTSIPAAFWYTIVTMTTLG>Y<GDMVPKTIAGKIFGSICSLSGVLVIALPVP403
KCND3-------SASKFTSIPASFWYTIVTMTTLG>Y<GDMVPKTIAGKIFGSICSLSGVLVIALPVP400
KCNF1-------PETLFKSIPQSFWWAIITMTTVG>Y<GDIYPKTTLGKLNAAISFLCGVIAIALPIH403
KCNG1---A---DSPEFTSIPACYWWAVITMTTVG>Y<GDMVPRSTPGQVVALSSILSGILLMAFPVT457
KCNG2---G---ARRDFSSVPASYWWAVISMTTVG>Y<GDMVPRSLPGQVVALSSILSGILLMAFPVT402
KCNG3---DLETSNKDFTSIPAACWWVIISMTTVG>Y<GDMYPITVPGRILGGVCVVSGIVLLALPIT406
KCNG4---G---RVLEFTSIPASYWWAIISMTTVG>Y<GDMVPRSVPGQMVALSSILSGILIMAFPAT451
KCNS1--------DVGFNTIPACWWWGTVSMTTVG>Y<GDVVPVTVAGKLAASGCILGGILVVALPIT454
KCNS2--------NEGLATIPACWWWATVSMTTVG>Y<GDVVPGTTAGKLTASACILAGILVVVLPIT407
KCNS3-------HTSSLTSIPICWWWATISMTTVG>Y<GDTHPVTLAGKLIASTCIICGILVVALPIT403
KCNV1-------PDTTFTSVPCAWWWATTSMTTVG>Y<GDIRPDTTTGKIVAFMCILSGILVLALPIA425
KCNV2-------PSTNFTTIPHSWWWAAVSISTVG>Y<GDMYPETHLGRFFAFLCIAFGIILNGMPIS490
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.Y315Cc.944A>G Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998 51(1):86-97. 9693036
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death. Clin Genet. 2003 63(4):273-82. 12702160
Inherited ArrhythmiaLQTS Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697
Inherited ArrhythmiaLQTS Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation. 2004 110(15):2119-24. 15466642
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999 99(4):529-33. 9927399
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS Mechanisms of I(Ks) suppression in LQT1 mutants. Am J Physiol Heart Circ Physiol. 2000 279(6):H3003-11. 11087258
p.Y315Fc.944A>T Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: possibly damaging
ReportsInherited ArrhythmiaLQTS Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS 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.Y315Sc.944A>C Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136
Inherited ArrhythmiaLQTS Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144
Inherited ArrhythmiaLQTS The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet. 2003 40(2):141-5. 12566525
Inherited ArrhythmiaLQTS Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest. 2008 118(6):2246-59. 18464931
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS 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.Y315Nc.943T>A Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS 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.Y315Hc.943T>C Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS 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