Paralogue Annotation for KCNQ1 residue 312

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 312
Reference Amino Acid: T - Threonine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 312

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2T277IEpileptic encephalopathy, early infantileHigh9 26544041
KCNA2T374AEpileptic encephalopathy, early onsetHigh9 27117551

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.



KCNQ1AVN-----ESGRVEFGSYADALWWGVVTVT>T<IGYGDKVPQTWVGKTIASCFSVFAISFFAL342
KCNQ2E----------NDHFDTYADALWWGLITLT>T<IGYGDKYPQTWNGRLLAATFTLIGVSFFAL307
KCNQ3VPEVDAQGEEMKEEFETYADALWWGLITLA>T<IGYGDKTPKTWEGRLIAATFSLIGVSFFAL346
KCNQ4A----------NSDFSSYADSLWWGTITLT>T<IGYGDKTPHTWLGRVLAAGFALLGISFFAL313
KCNQ5A----------NKEFSTYADALWWGTITLT>T<IGYGDKTPLTWLGRLLSAGFALLGISFFAL341
KCNA1E---------AESHFSSIPDAFWWAVVSMT>T<VGYGDMYPVTIGGKIVGSLCAIAGVLTIAL402
KCNA10E---------PESHFSSIPDGFWWAVVTMT>T<VGYGDMCPTTPGGKIVGTLCAIAGVLTIAL451
KCNA2E---------RESQFPSIPDAFWWAVVSMT>T<VGYGDMVPTTIGGKIVGSLCAIAGVLTIAL404
KCNA3D---------PTSGFSSIPDAFWWAVVTMT>T<VGYGDMHPVTIGGKIVGSLCAIAGVLTIAL474
KCNA4E---------PTTHFQSIPDAFWWAVVTMT>T<VGYGDMKPITVGGKIVGSLCAIAGVLTIAL554
KCNA5N---------QGTHFSSIPDAFWWAVVTMT>T<VGYGDMRPITVGGKIVGSLCAIAGVLTIAL510
KCNA6D---------DDSLFPSIPDAFWWAVVTMT>T<VGYGDMYPMTVGGKIVGSLCAIAGVLTIAL452
KCNA7R---------VDSHFTSIPESFWWAVVTMT>T<VGYGDMAPVTVGGKIVGSLCAIAGVLTISL388
KCNB1E---------DDTKFKSIPASFWWATITMT>T<VGYGDIYPKTLLGKIVGGLCCIAGVLVIAL407
KCNB2E---------DATKFTSIPASFWWATITMT>T<VGYGDIYPKTLLGKIVGGLCCIAGVLVIAL411
KCNC1GAQPNDPSASEHTHFKNIPIGFWWAVVTMT>T<LGYGDMYPQTWSGMLVGALCALAGVLTIAM430
KCNC2GAQPNDPSASEHTQFKNIPIGFWWAVVTMT>T<LGYGDMYPQTWSGMLVGALCALAGVLTIAM467
KCNC3GADPDDILGSNHTYFKNIPIGFWWAVVTMT>T<LGYGDMYPKTWSGMLVGALCALAGVLTIAM533
KCNC4GARPSDPRGNDHTDFKNIPIGFWWAVVTMT>T<LGYGDMYPKTWSGMLVGALCALAGVLTIAM466
KCND1T---------NKTNFTSIPAAFWYTIVTMT>T<LGYGDMVPSTIAGKIFGSICSLSGVLVIAL402
KCND2S---------SASKFTSIPAAFWYTIVTMT>T<LGYGDMVPKTIAGKIFGSICSLSGVLVIAL400
KCND3S---------SASKFTSIPASFWYTIVTMT>T<LGYGDMVPKTIAGKIFGSICSLSGVLVIAL397
KCNF1H---------PETLFKSIPQSFWWAIITMT>T<VGYGDIYPKTTLGKLNAAISFLCGVIAIAL400
KCNG1M-----A---DSPEFTSIPACYWWAVITMT>T<VGYGDMVPRSTPGQVVALSSILSGILLMAF454
KCNG2L-----G---ARRDFSSVPASYWWAVISMT>T<VGYGDMVPRSLPGQVVALSSILSGILLMAF399
KCNG3L-----DLETSNKDFTSIPAACWWVIISMT>T<VGYGDMYPITVPGRILGGVCVVSGIVLLAL403
KCNG4S-----G---RVLEFTSIPASYWWAIISMT>T<VGYGDMVPRSVPGQMVALSSILSGILIMAF448
KCNS1E----------DVGFNTIPACWWWGTVSMT>T<VGYGDVVPVTVAGKLAASGCILGGILVVAL451
KCNS2E----------NEGLATIPACWWWATVSMT>T<VGYGDVVPGTTAGKLTASACILAGILVVVL404
KCNS3D---------HTSSLTSIPICWWWATISMT>T<VGYGDTHPVTLAGKLIASTCIICGILVVAL400
KCNV1I---------PDTTFTSVPCAWWWATTSMT>T<VGYGDIRPDTTTGKIVAFMCILSGILVLAL422
KCNV2V---------PSTNFTTIPHSWWWAAVSIS>T<VGYGDMYPETHLGRFFAFLCIAFGIILNGM487
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.T312Ic.935C>T Inherited ArrhythmiaLQTSrs120074182SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244
Inherited ArrhythmiaLQTS Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome. Circulation. 1997 96(6):1733-6. 9323054
Inherited ArrhythmiaLQTS Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849
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 Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636
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 Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med. 2009 1(2):2ra6. 20368164
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 Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation. 2012 125(16):1988-96. 22456477
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
Other Cardiac Phenotype Whole-Exome Molecular Autopsy After Exertion-Related Sudden Unexplained Death in the Young. Circ Cardiovasc Genet. 2016 9(3):259-65. doi: 10.1161/CIRCGENETICS.115.001370. 27114410