Paralogue Annotation for KCNQ1 residue 269

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 269
Reference Amino Acid: G - Glycine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 269

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2G239REpileptic encephalopathy, early-onsetHigh9 23692823

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.



KCNQ1LHVDRQGGTWRLLGSVVFIHRQELITTLYI>G<FLGLIFSSYFVYLAEKDAVN-----ESGRV294
KCNQ2IRMDRRGGTWKLLGSVVYAHSKELVTAWYI>G<FLCLILASFLVYLAEKGE----------ND259
KCNQ3LRMDRRGGTWKLLGSAICAHSKELITAWYI>G<FLTLILSSFLVYLVEKDVPEVDAQGEEMKE298
KCNQ4VRMDRRGGTWKLLGSVVYAHSKELITAWYI>G<FLVLIFASFLVYLAEKDA----------NS265
KCNQ5VRMDRRGGTWKLLGSVVYAHSKELITAWYI>G<FLVLIFSSFLVYLVEKDA----------NK293
KCNA1FKLSRHSKGLQILGQTLKASMRELGLLIFF>L<FIGVILFSSAVYFAEAEE---------AES354
KCNA10FKLSRHSKGLQILGQTLKASMRELGLLIFF>L<FIGVILFSSAVYFAEVDE---------PES403
KCNA2FKLSRHSKGLQILGQTLKASMRELGLLIFF>L<FIGVILFSSAVYFAEADE---------RES356
KCNA3FKLSRHSKGLQILGQTLKASMRELGLLIFF>L<FIGVILFSSAVYFAEADD---------PTS426
KCNA4FKLSRHSKGLQILGHTLRASMRELGLLIFF>L<FIGVILFSSAVYFAEADE---------PTT506
KCNA5FKLSRHSKGLQILGKTLQASMRELGLLIFF>L<FIGVILFSSAVYFAEADN---------QGT462
KCNA6FKLSRHSKGLQILGKTLQASMRELGLLIFF>L<FIGVILFSSAVYFAEADD---------DDS404
KCNA7FKLSRHSKGLQILGQTLRASMRELGLLIFF>L<FIGVVLFSSAVYFAEVDR---------VDS340
KCNB1LKLARHSTGLQSLGFTLRRSYNELGLLILF>L<AMGIMIFSSLVFFAEKDE---------DDT359
KCNB2LKLARHSTGLQSLGFTLRRSYNELGLLILF>L<AMGIMIFSSLVFFAEKDE---------DAT363
KCNC1FKLTRHFVGLRVLGHTLRASTNEFLLLIIF>L<ALGVLIFATMIYYAERIGAQPNDPSASEHT382
KCNC2FKLTRHFVGLRVLGHTLRASTNEFLLLIIF>L<ALGVLIFATMIYYAERVGAQPNDPSASEHT419
KCNC3FKLTRHFVGLRVLGHTLRASTNEFLLLIIF>L<ALGVLIFATMIYYAERIGADPDDILGSNHT485
KCNC4FKLTRHFVGLRVLGHTLRASTNEFLLLIIF>L<ALGVLIFATMIYYAERIGARPSDPRGNDHT418
KCND1FKFSRHSQGLRILGYTLKSCASELGFLLFS>L<TMAIIIFATVMFYAEKGT---------NKT354
KCND2FKFSRHSQGLRILGYTLKSCASELGFLLFS>L<TMAIIIFATVMFYAEKGS---------SAS352
KCND3FKFSRHSQGLRILGYTLKSCASELGFLLFS>L<TMAIIIFATVMFYAEKGS---------SAS349
KCNF1FKLARHSSGLQTLTYALKRSFKELGLLLMY>L<AVGIFVFSALGYTMEQSH---------PET352
KCNG1MRLARHSLGLQTLGLTARRCTREFGLLLLF>L<CVAIALFAPLLYVIENEM-----A---DSP406
KCNG2MRLARHSLGLRSLGLTMRRCAREFGLLLLF>L<CVAMALFAPLVHLAEREL-----G---ARR351
KCNG3IKLARHFIGLQTLGLTLKRCYREMVMLLVF>I<CVAMAIFSALSQLLEHGL-----DLETSNK355
KCNG4MRLARHSLGLQTLGLTVRRCTREFGLLLLF>L<AVAITLFSPLVYVAEKES-----G---RVL400
KCNS1LKLARHSTGLRSLGATLKHSYREVGILLLY>L<AVGVSVFSGVAYTAEKEE----------DV403
KCNS2LKLARHSTGLRSLGATLKYSYKEVGLLLLY>L<SVGISIFSVVAYTIEKEE----------NE356
KCNS3LKLARHSVGLRSLGATLRHSYHEVGLLLLF>L<SVGISIFSVLIYSVEKDD---------HTS352
KCNV1LKLGRHSTGLRSLGMTITQCYEEVGLLLLF>L<SVGISIFSTVEYFAEQSI---------PDT374
KCNV2LKLARHSTGLRAFGFTLRQCYQQVGCLLLF>I<AMGIFTFSAAVYSVEHDV---------PST439
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G269Dc.806G>A Inherited ArrhythmiaLQTS,JLNSrs120074194SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136
Inherited ArrhythmiaLQTS Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849
Inherited ArrhythmiaJLNS Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. Mol Genet Metab. 2002 75(4):308-16. 12051962
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 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 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 Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 16(17):5472-9. 9312006
p.G269Sc.805G>A Inherited ArrhythmiaLQTSrs120074193SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc. 1999 74(11):1088-94. 10560595
Inherited ArrhythmiaLQTS Mutation in KCNQ1 that has both recessive and dominant characteristics. J Med Genet. 2002 39(9):681-5. 12205113
Inherited ArrhythmiaLQTS KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death. Clin Genet. 2003 63(4):273-82. 12702160
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 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 Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
Inherited ArrhythmiaLQTS Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. Scand J Clin Lab Invest. 2008 68(5):362-8. 18752142
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 9 KCNQ1 mutations associated with long-QT syndrome. Circ Arrhythm Electrophysiol. 2009 2(4):417-26. 19808498
Inherited ArrhythmiaLQTS Structural and functional changes in a synthetic S5 segment of KvLQT1 channel as a result of a conserved amino acid substitution that occurs in LQT1 syndrome of human. Biochim Biophys Acta. 2010 1798(3):461-70. 20044973
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
Inherited ArrhythmiaLQTS A molecular mechanism for adrenergic-induced long QT syndrome. J Am Coll Cardiol. 2014 63(8):819-27. doi: 10.1016/j.jacc.2013.08.1648. 24184248
p.Gly269Argc.805G>C UnknownSIFT:
Polyphen:
p.Gly269Valc.806G>T UnknownSIFT:
Polyphen: