Paralogue Annotation for KCNQ1 residue 305

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 305
Reference Amino Acid: W - Tryptophan
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 305

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ3W309REpilepsy, benign neonatalHigh9 10852552, 19167866, 18425618
KCNQ4W276SDeafness, autosomal dominant 2High9 10369879, 20832469, 20966080, 23750663, 26346818
KCNV2W450GCone dystrophy with supernormal rod ERGHigh9 17896311, 23115240
KCNV2W450RCone dystrophy with supernormal rod ERGHigh9 21882291
KCNQ4W276LHearing loss, non-syndromicHigh9 27068579

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.



KCNQ1VYLAEKDAVN-----ESGRVEFGSYADALW>W<GVVTVTTIGYGDKVPQTWVGKTIASCFSVF335
KCNQ2VYLAEKGE----------NDHFDTYADALW>W<GLITLTTIGYGDKYPQTWNGRLLAATFTLI300
KCNQ3VYLVEKDVPEVDAQGEEMKEEFETYADALW>W<GLITLATIGYGDKTPKTWEGRLIAATFSLI339
KCNQ4VYLAEKDA----------NSDFSSYADSLW>W<GTITLTTIGYGDKTPHTWLGRVLAAGFALL306
KCNQ5VYLVEKDA----------NKEFSTYADALW>W<GTITLTTIGYGDKTPLTWLGRLLSAGFALL334
KCNA1VYFAEAEE---------AESHFSSIPDAFW>W<AVVSMTTVGYGDMYPVTIGGKIVGSLCAIA395
KCNA10VYFAEVDE---------PESHFSSIPDGFW>W<AVVTMTTVGYGDMCPTTPGGKIVGTLCAIA444
KCNA2VYFAEADE---------RESQFPSIPDAFW>W<AVVSMTTVGYGDMVPTTIGGKIVGSLCAIA397
KCNA3VYFAEADD---------PTSGFSSIPDAFW>W<AVVTMTTVGYGDMHPVTIGGKIVGSLCAIA467
KCNA4VYFAEADE---------PTTHFQSIPDAFW>W<AVVTMTTVGYGDMKPITVGGKIVGSLCAIA547
KCNA5VYFAEADN---------QGTHFSSIPDAFW>W<AVVTMTTVGYGDMRPITVGGKIVGSLCAIA503
KCNA6VYFAEADD---------DDSLFPSIPDAFW>W<AVVTMTTVGYGDMYPMTVGGKIVGSLCAIA445
KCNA7VYFAEVDR---------VDSHFTSIPESFW>W<AVVTMTTVGYGDMAPVTVGGKIVGSLCAIA381
KCNB1VFFAEKDE---------DDTKFKSIPASFW>W<ATITMTTVGYGDIYPKTLLGKIVGGLCCIA400
KCNB2VFFAEKDE---------DATKFTSIPASFW>W<ATITMTTVGYGDIYPKTLLGKIVGGLCCIA404
KCNC1IYYAERIGAQPNDPSASEHTHFKNIPIGFW>W<AVVTMTTLGYGDMYPQTWSGMLVGALCALA423
KCNC2IYYAERVGAQPNDPSASEHTQFKNIPIGFW>W<AVVTMTTLGYGDMYPQTWSGMLVGALCALA460
KCNC3IYYAERIGADPDDILGSNHTYFKNIPIGFW>W<AVVTMTTLGYGDMYPKTWSGMLVGALCALA526
KCNC4IYYAERIGARPSDPRGNDHTDFKNIPIGFW>W<AVVTMTTLGYGDMYPKTWSGMLVGALCALA459
KCND1MFYAEKGT---------NKTNFTSIPAAFW>Y<TIVTMTTLGYGDMVPSTIAGKIFGSICSLS395
KCND2MFYAEKGS---------SASKFTSIPAAFW>Y<TIVTMTTLGYGDMVPKTIAGKIFGSICSLS393
KCND3MFYAEKGS---------SASKFTSIPASFW>Y<TIVTMTTLGYGDMVPKTIAGKIFGSICSLS390
KCNF1GYTMEQSH---------PETLFKSIPQSFW>W<AIITMTTVGYGDIYPKTTLGKLNAAISFLC393
KCNG1LYVIENEM-----A---DSPEFTSIPACYW>W<AVITMTTVGYGDMVPRSTPGQVVALSSILS447
KCNG2VHLAEREL-----G---ARRDFSSVPASYW>W<AVISMTTVGYGDMVPRSLPGQVVALSSILS392
KCNG3SQLLEHGL-----DLETSNKDFTSIPAACW>W<VIISMTTVGYGDMYPITVPGRILGGVCVVS396
KCNG4VYVAEKES-----G---RVLEFTSIPASYW>W<AIISMTTVGYGDMVPRSVPGQMVALSSILS441
KCNS1AYTAEKEE----------DVGFNTIPACWW>W<GTVSMTTVGYGDVVPVTVAGKLAASGCILG444
KCNS2AYTIEKEE----------NEGLATIPACWW>W<ATVSMTTVGYGDVVPGTTAGKLTASACILA397
KCNS3IYSVEKDD---------HTSSLTSIPICWW>W<ATISMTTVGYGDTHPVTLAGKLIASTCIIC393
KCNV1EYFAEQSI---------PDTTFTSVPCAWW>W<ATTSMTTVGYGDIRPDTTTGKIVAFMCILS415
KCNV2VYSVEHDV---------PSTNFTTIPHSWW>W<AAVSISTVGYGDMYPETHLGRFFAFLCIAF480
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.W305Rc.913T>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
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
p.W305Sc.914G>C Inherited ArrhythmiaLQTS,JLNSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaJLNS Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome. Eur J Hum Genet. 1998 6(2):129-33. 9781056
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 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
Inherited ArrhythmiaLQTS Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538
p.W305Lc.914G>T Inherited ArrhythmiaSIFT:
Polyphen:
ReportsInherited ArrhythmiaLQTS Genotype-based clinical manifestation and treatment of Chinese long QT syndrome patients with KCNQ1 mutations - R380S and W305L. Cardiol Young. 2016 26(4):754-63. doi: 10.1017/S1047951115001304. 26344792