Paralogue Annotation for KCNQ1 residue 325

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 325
Reference Amino Acid: G - Glycine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 325

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ4G296SDeafness, autosomal dominant 2High9 18030493, 20966080, 23750663
KCNQ2G290DEpileptic encephalopathy, neonatalHigh9 22275249, 24318194
KCNQ2G290SEpileptic encephalopathy, early-onsetHigh9 23692823, 23621294
KCNV2G470DCone-rod dystrophyHigh9 26992781

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.



KCNQ1EFGSYADALWWGVVTVTTIGYGDKVPQTWV>G<KTIASCFSVFAISFFALPAGILGSGFALKV355
KCNQ2HFDTYADALWWGLITLTTIGYGDKYPQTWN>G<RLLAATFTLIGVSFFALPAGILGSGFALKV320
KCNQ3EFETYADALWWGLITLATIGYGDKTPKTWE>G<RLIAATFSLIGVSFFALPAGILGSGLALKV359
KCNQ4DFSSYADSLWWGTITLTTIGYGDKTPHTWL>G<RVLAAGFALLGISFFALPAGILGSGFALKV326
KCNQ5EFSTYADALWWGTITLTTIGYGDKTPLTWL>G<RLLSAGFALLGISFFALPAGILGSGFALKV354
KCNA1HFSSIPDAFWWAVVSMTTVGYGDMYPVTIG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY415
KCNA10HFSSIPDGFWWAVVTMTTVGYGDMCPTTPG>G<KIVGTLCAIAGVLTIALPVPVIVSNFNYFY464
KCNA2QFPSIPDAFWWAVVSMTTVGYGDMVPTTIG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY417
KCNA3GFSSIPDAFWWAVVTMTTVGYGDMHPVTIG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY487
KCNA4HFQSIPDAFWWAVVTMTTVGYGDMKPITVG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY567
KCNA5HFSSIPDAFWWAVVTMTTVGYGDMRPITVG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY523
KCNA6LFPSIPDAFWWAVVTMTTVGYGDMYPMTVG>G<KIVGSLCAIAGVLTIALPVPVIVSNFNYFY465
KCNA7HFTSIPESFWWAVVTMTTVGYGDMAPVTVG>G<KIVGSLCAIAGVLTISLPVPVIVSNFSYFY401
KCNB1KFKSIPASFWWATITMTTVGYGDIYPKTLL>G<KIVGGLCCIAGVLVIALPIPIIVNNFSEFY420
KCNB2KFTSIPASFWWATITMTTVGYGDIYPKTLL>G<KIVGGLCCIAGVLVIALPIPIIVNNFSEFY424
KCNC1HFKNIPIGFWWAVVTMTTLGYGDMYPQTWS>G<MLVGALCALAGVLTIAMPVPVIVNNFGMYY443
KCNC2QFKNIPIGFWWAVVTMTTLGYGDMYPQTWS>G<MLVGALCALAGVLTIAMPVPVIVNNFGMYY480
KCNC3YFKNIPIGFWWAVVTMTTLGYGDMYPKTWS>G<MLVGALCALAGVLTIAMPVPVIVNNFGMYY546
KCNC4DFKNIPIGFWWAVVTMTTLGYGDMYPKTWS>G<MLVGALCALAGVLTIAMPVPVIVNNFGMYY479
KCND1NFTSIPAAFWYTIVTMTTLGYGDMVPSTIA>G<KIFGSICSLSGVLVIALPVPVIVSNFSRIY415
KCND2KFTSIPAAFWYTIVTMTTLGYGDMVPKTIA>G<KIFGSICSLSGVLVIALPVPVIVSNFSRIY413
KCND3KFTSIPASFWYTIVTMTTLGYGDMVPKTIA>G<KIFGSICSLSGVLVIALPVPVIVSNFSRIY410
KCNF1LFKSIPQSFWWAIITMTTVGYGDIYPKTTL>G<KLNAAISFLCGVIAIALPIHPIINNFVRYY413
KCNG1EFTSIPACYWWAVITMTTVGYGDMVPRSTP>G<QVVALSSILSGILLMAFPVTSIFHTFSRSY467
KCNG2DFSSVPASYWWAVISMTTVGYGDMVPRSLP>G<QVVALSSILSGILLMAFPVTSIFHTFSRSY412
KCNG3DFTSIPAACWWVIISMTTVGYGDMYPITVP>G<RILGGVCVVSGIVLLALPITFIYHSFVQCY416
KCNG4EFTSIPASYWWAIISMTTVGYGDMVPRSVP>G<QMVALSSILSGILIMAFPATSIFHTFSHSY461
KCNS1GFNTIPACWWWGTVSMTTVGYGDVVPVTVA>G<KLAASGCILGGILVVALPITIIFNKFSHFY464
KCNS2GLATIPACWWWATVSMTTVGYGDVVPGTTA>G<KLTASACILAGILVVVLPITLIFNKFSHFY417
KCNS3SLTSIPICWWWATISMTTVGYGDTHPVTLA>G<KLIASTCIICGILVVALPITIIFNKFSKYY413
KCNV1TFTSVPCAWWWATTSMTTVGYGDIRPDTTT>G<KIVAFMCILSGILVLALPIAIINDRFSACY435
KCNV2NFTTIPHSWWWAAVSISTVGYGDMYPETHL>G<RFFAFLCIAFGIILNGMPISILYNKFSDYY500
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G325Rc.973G>A Inherited ArrhythmiaLQTSrs199472756SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation. 1997 95(3):565-7. 9024139
Inherited 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 ArrhythmiaLQTS Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Hum Mutat. 2001 18(5):451-7. 11668638
Other Cardiac Phenotype Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol. 2004 43(5):826-30. 14998624
Inherited ArrhythmiaLQTS Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
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 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 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 ArrhythmiaLQTS Impaired ion channel function related to a common KCNQ1 mutation - implications for risk stratification in long QT syndrome 1. Gene. 2012 511(1):26-33. doi: 10.1016/j.gene.2012.09.041. 23000022
Inherited ArrhythmiaLQTS High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation. Biochemistry. 2012 51(45):9076-85. doi: 10.1021/bi3009449. 23092362
p.G325Ec.974G>A Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome. Circ Arrhythm Electrophysiol. 2011 4(6):867-73. 21956039
p.G325Wc.973G>T Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing. BMC Cardiovasc Disord. 2012 12:95. doi: 10.1186/1471-2261-12-95. 23098067
p.G325Rc.973G>C Inherited ArrhythmiaLQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol. 2012 60(24):2515-24. doi: 10.1016/j.jacc.2012.08.1009. 23158531