Paralogue Annotation for KCNQ1 residue 273

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 273
Reference Amino Acid: L - Leucine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 273

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2L243FEpilepsy, benign neonatalHigh9 14534157

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.



KCNQ1RQGGTWRLLGSVVFIHRQELITTLYIGFLG>L<IFSSYFVYLAEKDAVN-----ESGRVEFGS298
KCNQ2RRGGTWKLLGSVVYAHSKELVTAWYIGFLC>L<ILASFLVYLAEKGE----------NDHFDT263
KCNQ3RRGGTWKLLGSAICAHSKELITAWYIGFLT>L<ILSSFLVYLVEKDVPEVDAQGEEMKEEFET302
KCNQ4RRGGTWKLLGSVVYAHSKELITAWYIGFLV>L<IFASFLVYLAEKDA----------NSDFSS269
KCNQ5RRGGTWKLLGSVVYAHSKELITAWYIGFLV>L<IFSSFLVYLVEKDA----------NKEFST297
KCNA1RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEAEE---------AESHFSS358
KCNA10RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEVDE---------PESHFSS407
KCNA2RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEADE---------RESQFPS360
KCNA3RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEADD---------PTSGFSS430
KCNA4RHSKGLQILGHTLRASMRELGLLIFFLFIG>V<ILFSSAVYFAEADE---------PTTHFQS510
KCNA5RHSKGLQILGKTLQASMRELGLLIFFLFIG>V<ILFSSAVYFAEADN---------QGTHFSS466
KCNA6RHSKGLQILGKTLQASMRELGLLIFFLFIG>V<ILFSSAVYFAEADD---------DDSLFPS408
KCNA7RHSKGLQILGQTLRASMRELGLLIFFLFIG>V<VLFSSAVYFAEVDR---------VDSHFTS344
KCNB1RHSTGLQSLGFTLRRSYNELGLLILFLAMG>I<MIFSSLVFFAEKDE---------DDTKFKS363
KCNB2RHSTGLQSLGFTLRRSYNELGLLILFLAMG>I<MIFSSLVFFAEKDE---------DATKFTS367
KCNC1RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGAQPNDPSASEHTHFKN386
KCNC2RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERVGAQPNDPSASEHTQFKN423
KCNC3RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGADPDDILGSNHTYFKN489
KCNC4RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGARPSDPRGNDHTDFKN422
KCND1RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGT---------NKTNFTS358
KCND2RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGS---------SASKFTS356
KCND3RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGS---------SASKFTS353
KCNF1RHSSGLQTLTYALKRSFKELGLLLMYLAVG>I<FVFSALGYTMEQSH---------PETLFKS356
KCNG1RHSLGLQTLGLTARRCTREFGLLLLFLCVA>I<ALFAPLLYVIENEM-----A---DSPEFTS410
KCNG2RHSLGLRSLGLTMRRCAREFGLLLLFLCVA>M<ALFAPLVHLAEREL-----G---ARRDFSS355
KCNG3RHFIGLQTLGLTLKRCYREMVMLLVFICVA>M<AIFSALSQLLEHGL-----DLETSNKDFTS359
KCNG4RHSLGLQTLGLTVRRCTREFGLLLLFLAVA>I<TLFSPLVYVAEKES-----G---RVLEFTS404
KCNS1RHSTGLRSLGATLKHSYREVGILLLYLAVG>V<SVFSGVAYTAEKEE----------DVGFNT407
KCNS2RHSTGLRSLGATLKYSYKEVGLLLLYLSVG>I<SIFSVVAYTIEKEE----------NEGLAT360
KCNS3RHSVGLRSLGATLRHSYHEVGLLLLFLSVG>I<SIFSVLIYSVEKDD---------HTSSLTS356
KCNV1RHSTGLRSLGMTITQCYEEVGLLLLFLSVG>I<SIFSTVEYFAEQSI---------PDTTFTS378
KCNV2RHSTGLRAFGFTLRQCYQQVGCLLLFIAMG>I<FTFSAAVYSVEHDV---------PSTNFTT443
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.L273Fc.817C>T Inherited ArrhythmiaLQTS,JLNSSIFT: 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 A founder mutation of the potassium channel KCNQ1 in long QT syndrome: implications for estimation of disease prevalence and molecular diagnostics. J Am Coll Cardiol. 2001 37(2):562-8. 11216980
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 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 of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724
Inherited ArrhythmiaLQTS Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology. Med Biol Eng Comput. 2006 44(7):543-9. 16937190
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 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 Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc Res. 2005 67(3):476-86. 15935335
Inherited ArrhythmiaLQTS Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome. J Biol Chem. 2001 276(17):13600-5. 11278406
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
Inherited ArrhythmiaJLNS Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia. Clin Genet. 2015 87(1):74-9. doi: 10.1111/cge.12330. 24372464
Inherited ArrhythmiaLQTS Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant. Seizure. 2015 25:65-7. doi: 10.1016/j.seizure.2015.01.003. 25645639
p.L273Rc.818T>G Inherited ArrhythmiaLQTSSIFT: 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