Paralogue Annotation for KCNQ1 residue 303

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 303
Reference Amino Acid: L - Leucine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 303

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ4L274HDeafness, autosomal dominant 2High9 10925378, 20966080, 23750663
KCNQ2L268FEpileptic encephalopathy, early-onsetHigh9 25880994

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.



KCNQ1YFVYLAEKDAVN-----ESGRVEFGSYADA>L<WWGVVTVTTIGYGDKVPQTWVGKTIASCFS333
KCNQ2FLVYLAEKGE----------NDHFDTYADA>L<WWGLITLTTIGYGDKYPQTWNGRLLAATFT298
KCNQ3FLVYLVEKDVPEVDAQGEEMKEEFETYADA>L<WWGLITLATIGYGDKTPKTWEGRLIAATFS337
KCNQ4FLVYLAEKDA----------NSDFSSYADS>L<WWGTITLTTIGYGDKTPHTWLGRVLAAGFA304
KCNQ5FLVYLVEKDA----------NKEFSTYADA>L<WWGTITLTTIGYGDKTPLTWLGRLLSAGFA332
KCNA1SAVYFAEAEE---------AESHFSSIPDA>F<WWAVVSMTTVGYGDMYPVTIGGKIVGSLCA393
KCNA10SAVYFAEVDE---------PESHFSSIPDG>F<WWAVVTMTTVGYGDMCPTTPGGKIVGTLCA442
KCNA2SAVYFAEADE---------RESQFPSIPDA>F<WWAVVSMTTVGYGDMVPTTIGGKIVGSLCA395
KCNA3SAVYFAEADD---------PTSGFSSIPDA>F<WWAVVTMTTVGYGDMHPVTIGGKIVGSLCA465
KCNA4SAVYFAEADE---------PTTHFQSIPDA>F<WWAVVTMTTVGYGDMKPITVGGKIVGSLCA545
KCNA5SAVYFAEADN---------QGTHFSSIPDA>F<WWAVVTMTTVGYGDMRPITVGGKIVGSLCA501
KCNA6SAVYFAEADD---------DDSLFPSIPDA>F<WWAVVTMTTVGYGDMYPMTVGGKIVGSLCA443
KCNA7SAVYFAEVDR---------VDSHFTSIPES>F<WWAVVTMTTVGYGDMAPVTVGGKIVGSLCA379
KCNB1SLVFFAEKDE---------DDTKFKSIPAS>F<WWATITMTTVGYGDIYPKTLLGKIVGGLCC398
KCNB2SLVFFAEKDE---------DATKFTSIPAS>F<WWATITMTTVGYGDIYPKTLLGKIVGGLCC402
KCNC1TMIYYAERIGAQPNDPSASEHTHFKNIPIG>F<WWAVVTMTTLGYGDMYPQTWSGMLVGALCA421
KCNC2TMIYYAERVGAQPNDPSASEHTQFKNIPIG>F<WWAVVTMTTLGYGDMYPQTWSGMLVGALCA458
KCNC3TMIYYAERIGADPDDILGSNHTYFKNIPIG>F<WWAVVTMTTLGYGDMYPKTWSGMLVGALCA524
KCNC4TMIYYAERIGARPSDPRGNDHTDFKNIPIG>F<WWAVVTMTTLGYGDMYPKTWSGMLVGALCA457
KCND1TVMFYAEKGT---------NKTNFTSIPAA>F<WYTIVTMTTLGYGDMVPSTIAGKIFGSICS393
KCND2TVMFYAEKGS---------SASKFTSIPAA>F<WYTIVTMTTLGYGDMVPKTIAGKIFGSICS391
KCND3TVMFYAEKGS---------SASKFTSIPAS>F<WYTIVTMTTLGYGDMVPKTIAGKIFGSICS388
KCNF1ALGYTMEQSH---------PETLFKSIPQS>F<WWAIITMTTVGYGDIYPKTTLGKLNAAISF391
KCNG1PLLYVIENEM-----A---DSPEFTSIPAC>Y<WWAVITMTTVGYGDMVPRSTPGQVVALSSI445
KCNG2PLVHLAEREL-----G---ARRDFSSVPAS>Y<WWAVISMTTVGYGDMVPRSLPGQVVALSSI390
KCNG3ALSQLLEHGL-----DLETSNKDFTSIPAA>C<WWVIISMTTVGYGDMYPITVPGRILGGVCV394
KCNG4PLVYVAEKES-----G---RVLEFTSIPAS>Y<WWAIISMTTVGYGDMVPRSVPGQMVALSSI439
KCNS1GVAYTAEKEE----------DVGFNTIPAC>W<WWGTVSMTTVGYGDVVPVTVAGKLAASGCI442
KCNS2VVAYTIEKEE----------NEGLATIPAC>W<WWATVSMTTVGYGDVVPGTTAGKLTASACI395
KCNS3VLIYSVEKDD---------HTSSLTSIPIC>W<WWATISMTTVGYGDTHPVTLAGKLIASTCI391
KCNV1TVEYFAEQSI---------PDTTFTSVPCA>W<WWATTSMTTVGYGDIRPDTTTGKIVAFMCI413
KCNV2AAVYSVEHDV---------PSTNFTTIPHS>W<WWAAVSISTVGYGDMYPETHLGRFFAFLCI478
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.L303Pc.908T>C Inherited ArrhythmiaLQTSrs199472740SIFT: deleterious
Polyphen: probably damaging
ReportsInherited 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
p.L303Rc.908T>G Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction. Eur J Hum Genet. 2016 24(8):1160-6. doi: 10.1038/ejhg.2015.257. 26669661