Paralogue Annotation for KCNQ1 residue 304

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 304
Reference Amino Acid: W - Tryptophan
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 304

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ4W275RHearing loss, non-syndromic, autosomal dominantHigh9 25116015

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.



KCNQ1FVYLAEKDAVN-----ESGRVEFGSYADAL>W<WGVVTVTTIGYGDKVPQTWVGKTIASCFSV334
KCNQ2LVYLAEKGE----------NDHFDTYADAL>W<WGLITLTTIGYGDKYPQTWNGRLLAATFTL299
KCNQ3LVYLVEKDVPEVDAQGEEMKEEFETYADAL>W<WGLITLATIGYGDKTPKTWEGRLIAATFSL338
KCNQ4LVYLAEKDA----------NSDFSSYADSL>W<WGTITLTTIGYGDKTPHTWLGRVLAAGFAL305
KCNQ5LVYLVEKDA----------NKEFSTYADAL>W<WGTITLTTIGYGDKTPLTWLGRLLSAGFAL333
KCNA1AVYFAEAEE---------AESHFSSIPDAF>W<WAVVSMTTVGYGDMYPVTIGGKIVGSLCAI394
KCNA10AVYFAEVDE---------PESHFSSIPDGF>W<WAVVTMTTVGYGDMCPTTPGGKIVGTLCAI443
KCNA2AVYFAEADE---------RESQFPSIPDAF>W<WAVVSMTTVGYGDMVPTTIGGKIVGSLCAI396
KCNA3AVYFAEADD---------PTSGFSSIPDAF>W<WAVVTMTTVGYGDMHPVTIGGKIVGSLCAI466
KCNA4AVYFAEADE---------PTTHFQSIPDAF>W<WAVVTMTTVGYGDMKPITVGGKIVGSLCAI546
KCNA5AVYFAEADN---------QGTHFSSIPDAF>W<WAVVTMTTVGYGDMRPITVGGKIVGSLCAI502
KCNA6AVYFAEADD---------DDSLFPSIPDAF>W<WAVVTMTTVGYGDMYPMTVGGKIVGSLCAI444
KCNA7AVYFAEVDR---------VDSHFTSIPESF>W<WAVVTMTTVGYGDMAPVTVGGKIVGSLCAI380
KCNB1LVFFAEKDE---------DDTKFKSIPASF>W<WATITMTTVGYGDIYPKTLLGKIVGGLCCI399
KCNB2LVFFAEKDE---------DATKFTSIPASF>W<WATITMTTVGYGDIYPKTLLGKIVGGLCCI403
KCNC1MIYYAERIGAQPNDPSASEHTHFKNIPIGF>W<WAVVTMTTLGYGDMYPQTWSGMLVGALCAL422
KCNC2MIYYAERVGAQPNDPSASEHTQFKNIPIGF>W<WAVVTMTTLGYGDMYPQTWSGMLVGALCAL459
KCNC3MIYYAERIGADPDDILGSNHTYFKNIPIGF>W<WAVVTMTTLGYGDMYPKTWSGMLVGALCAL525
KCNC4MIYYAERIGARPSDPRGNDHTDFKNIPIGF>W<WAVVTMTTLGYGDMYPKTWSGMLVGALCAL458
KCND1VMFYAEKGT---------NKTNFTSIPAAF>W<YTIVTMTTLGYGDMVPSTIAGKIFGSICSL394
KCND2VMFYAEKGS---------SASKFTSIPAAF>W<YTIVTMTTLGYGDMVPKTIAGKIFGSICSL392
KCND3VMFYAEKGS---------SASKFTSIPASF>W<YTIVTMTTLGYGDMVPKTIAGKIFGSICSL389
KCNF1LGYTMEQSH---------PETLFKSIPQSF>W<WAIITMTTVGYGDIYPKTTLGKLNAAISFL392
KCNG1LLYVIENEM-----A---DSPEFTSIPACY>W<WAVITMTTVGYGDMVPRSTPGQVVALSSIL446
KCNG2LVHLAEREL-----G---ARRDFSSVPASY>W<WAVISMTTVGYGDMVPRSLPGQVVALSSIL391
KCNG3LSQLLEHGL-----DLETSNKDFTSIPAAC>W<WVIISMTTVGYGDMYPITVPGRILGGVCVV395
KCNG4LVYVAEKES-----G---RVLEFTSIPASY>W<WAIISMTTVGYGDMVPRSVPGQMVALSSIL440
KCNS1VAYTAEKEE----------DVGFNTIPACW>W<WGTVSMTTVGYGDVVPVTVAGKLAASGCIL443
KCNS2VAYTIEKEE----------NEGLATIPACW>W<WATVSMTTVGYGDVVPGTTAGKLTASACIL396
KCNS3LIYSVEKDD---------HTSSLTSIPICW>W<WATISMTTVGYGDTHPVTLAGKLIASTCII392
KCNV1VEYFAEQSI---------PDTTFTSVPCAW>W<WATTSMTTVGYGDIRPDTTTGKIVAFMCIL414
KCNV2AVYSVEHDV---------PSTNFTTIPHSW>W<WAAVSISTVGYGDMYPETHLGRFFAFLCIA479
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.W304Rc.910T>C Inherited ArrhythmiaLQTSrs199473466SIFT: deleterious
Polyphen: probably damaging
ReportsInherited 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 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