Paralogue Annotation for KCNQ1 residue 277

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 277
Reference Amino Acid: S - Serine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 277

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2S247WEpilepsy, benign neonatalHigh9 12742592

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.



KCNQ1TWRLLGSVVFIHRQELITTLYIGFLGLIFS>S<YFVYLAEKDAVN-----ESGRVEFGSYADA302
KCNQ2TWKLLGSVVYAHSKELVTAWYIGFLCLILA>S<FLVYLAEKGE----------NDHFDTYADA267
KCNQ3TWKLLGSAICAHSKELITAWYIGFLTLILS>S<FLVYLVEKDVPEVDAQGEEMKEEFETYADA306
KCNQ4TWKLLGSVVYAHSKELITAWYIGFLVLIFA>S<FLVYLAEKDA----------NSDFSSYADS273
KCNQ5TWKLLGSVVYAHSKELITAWYIGFLVLIFS>S<FLVYLVEKDA----------NKEFSTYADA301
KCNA1GLQILGQTLKASMRELGLLIFFLFIGVILF>S<SAVYFAEAEE---------AESHFSSIPDA362
KCNA10GLQILGQTLKASMRELGLLIFFLFIGVILF>S<SAVYFAEVDE---------PESHFSSIPDG411
KCNA2GLQILGQTLKASMRELGLLIFFLFIGVILF>S<SAVYFAEADE---------RESQFPSIPDA364
KCNA3GLQILGQTLKASMRELGLLIFFLFIGVILF>S<SAVYFAEADD---------PTSGFSSIPDA434
KCNA4GLQILGHTLRASMRELGLLIFFLFIGVILF>S<SAVYFAEADE---------PTTHFQSIPDA514
KCNA5GLQILGKTLQASMRELGLLIFFLFIGVILF>S<SAVYFAEADN---------QGTHFSSIPDA470
KCNA6GLQILGKTLQASMRELGLLIFFLFIGVILF>S<SAVYFAEADD---------DDSLFPSIPDA412
KCNA7GLQILGQTLRASMRELGLLIFFLFIGVVLF>S<SAVYFAEVDR---------VDSHFTSIPES348
KCNB1GLQSLGFTLRRSYNELGLLILFLAMGIMIF>S<SLVFFAEKDE---------DDTKFKSIPAS367
KCNB2GLQSLGFTLRRSYNELGLLILFLAMGIMIF>S<SLVFFAEKDE---------DATKFTSIPAS371
KCNC1GLRVLGHTLRASTNEFLLLIIFLALGVLIF>A<TMIYYAERIGAQPNDPSASEHTHFKNIPIG390
KCNC2GLRVLGHTLRASTNEFLLLIIFLALGVLIF>A<TMIYYAERVGAQPNDPSASEHTQFKNIPIG427
KCNC3GLRVLGHTLRASTNEFLLLIIFLALGVLIF>A<TMIYYAERIGADPDDILGSNHTYFKNIPIG493
KCNC4GLRVLGHTLRASTNEFLLLIIFLALGVLIF>A<TMIYYAERIGARPSDPRGNDHTDFKNIPIG426
KCND1GLRILGYTLKSCASELGFLLFSLTMAIIIF>A<TVMFYAEKGT---------NKTNFTSIPAA362
KCND2GLRILGYTLKSCASELGFLLFSLTMAIIIF>A<TVMFYAEKGS---------SASKFTSIPAA360
KCND3GLRILGYTLKSCASELGFLLFSLTMAIIIF>A<TVMFYAEKGS---------SASKFTSIPAS357
KCNF1GLQTLTYALKRSFKELGLLLMYLAVGIFVF>S<ALGYTMEQSH---------PETLFKSIPQS360
KCNG1GLQTLGLTARRCTREFGLLLLFLCVAIALF>A<PLLYVIENEM-----A---DSPEFTSIPAC414
KCNG2GLRSLGLTMRRCAREFGLLLLFLCVAMALF>A<PLVHLAEREL-----G---ARRDFSSVPAS359
KCNG3GLQTLGLTLKRCYREMVMLLVFICVAMAIF>S<ALSQLLEHGL-----DLETSNKDFTSIPAA363
KCNG4GLQTLGLTVRRCTREFGLLLLFLAVAITLF>S<PLVYVAEKES-----G---RVLEFTSIPAS408
KCNS1GLRSLGATLKHSYREVGILLLYLAVGVSVF>S<GVAYTAEKEE----------DVGFNTIPAC411
KCNS2GLRSLGATLKYSYKEVGLLLLYLSVGISIF>S<VVAYTIEKEE----------NEGLATIPAC364
KCNS3GLRSLGATLRHSYHEVGLLLLFLSVGISIF>S<VLIYSVEKDD---------HTSSLTSIPIC360
KCNV1GLRSLGMTITQCYEEVGLLLLFLSVGISIF>S<TVEYFAEQSI---------PDTTFTSVPCA382
KCNV2GLRAFGFTLRQCYQQVGCLLLFIAMGIFTF>S<AAVYSVEHDV---------PSTNFTTIPHS447
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.S277Lc.830C>T Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population. Hum Mutat. 2002 20(6):475-6. 12442276
Inherited ArrhythmiaLQTS [The mutation scanning of KCNQ1 gene for 31 long QT syndrome families]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 21(3):236-9. 15192825
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 [Novel mutations of potassium channel KCNQ1 S145L and KCNH2 Y475C genes in Chinese pedigrees of long QT syndrome]. Zhonghua Nei Ke Za Zhi. 2006 45(6):463-6. 16831322
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 Biophysical properties of mutant KCNQ1 S277L channels linked to hereditary long QT syndrome with phenotypic variability. Biochim Biophys Acta. 2011 1812(4):488-94. 21241800
Inherited ArrhythmiaLQTS A dual mechanism for I(Ks) current reduction by the pathogenic mutation KCNQ1-S277L. Pacing Clin Electrophysiol. 2011 34(12):1652-64. doi: 10.1111/j.1540-8159.2011.0319 21895724
Inherited ArrhythmiaLQTS 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 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
p.S277Pc.829T>C Inherited ArrhythmiaLQTSSIFT: 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.S277Wc.830C>G Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944