| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ3 | W309R | Epilepsy, benign neonatal | High | 9 | 10852552, 19167866, 18425618 |
| KCNQ4 | W276S | Deafness, autosomal dominant 2 | High | 9 | 10369879, 20832469, 20966080, 23750663, 26346818 |
| KCNV2 | W450G | Cone dystrophy with supernormal rod ERG | High | 9 | 17896311, 23115240 |
| KCNV2 | W450R | Cone dystrophy with supernormal rod ERG | High | 9 | 21882291 |
| KCNQ4 | W276L | Hearing loss, non-syndromic | High | 9 | 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.
| KCNQ1 | VYLAEKDAVN-----ESGRVEFGSYADALW>W<GVVTVTTIGYGDKVPQTWVGKTIASCFSVF | 335 |
| KCNQ2 | VYLAEKGE----------NDHFDTYADALW>W<GLITLTTIGYGDKYPQTWNGRLLAATFTLI | 300 |
| KCNQ3 | VYLVEKDVPEVDAQGEEMKEEFETYADALW>W<GLITLATIGYGDKTPKTWEGRLIAATFSLI | 339 |
| KCNQ4 | VYLAEKDA----------NSDFSSYADSLW>W<GTITLTTIGYGDKTPHTWLGRVLAAGFALL | 306 |
| KCNQ5 | VYLVEKDA----------NKEFSTYADALW>W<GTITLTTIGYGDKTPLTWLGRLLSAGFALL | 334 |
| KCNA1 | VYFAEAEE---------AESHFSSIPDAFW>W<AVVSMTTVGYGDMYPVTIGGKIVGSLCAIA | 395 |
| KCNA10 | VYFAEVDE---------PESHFSSIPDGFW>W<AVVTMTTVGYGDMCPTTPGGKIVGTLCAIA | 444 |
| KCNA2 | VYFAEADE---------RESQFPSIPDAFW>W<AVVSMTTVGYGDMVPTTIGGKIVGSLCAIA | 397 |
| KCNA3 | VYFAEADD---------PTSGFSSIPDAFW>W<AVVTMTTVGYGDMHPVTIGGKIVGSLCAIA | 467 |
| KCNA4 | VYFAEADE---------PTTHFQSIPDAFW>W<AVVTMTTVGYGDMKPITVGGKIVGSLCAIA | 547 |
| KCNA5 | VYFAEADN---------QGTHFSSIPDAFW>W<AVVTMTTVGYGDMRPITVGGKIVGSLCAIA | 503 |
| KCNA6 | VYFAEADD---------DDSLFPSIPDAFW>W<AVVTMTTVGYGDMYPMTVGGKIVGSLCAIA | 445 |
| KCNA7 | VYFAEVDR---------VDSHFTSIPESFW>W<AVVTMTTVGYGDMAPVTVGGKIVGSLCAIA | 381 |
| KCNB1 | VFFAEKDE---------DDTKFKSIPASFW>W<ATITMTTVGYGDIYPKTLLGKIVGGLCCIA | 400 |
| KCNB2 | VFFAEKDE---------DATKFTSIPASFW>W<ATITMTTVGYGDIYPKTLLGKIVGGLCCIA | 404 |
| KCNC1 | IYYAERIGAQPNDPSASEHTHFKNIPIGFW>W<AVVTMTTLGYGDMYPQTWSGMLVGALCALA | 423 |
| KCNC2 | IYYAERVGAQPNDPSASEHTQFKNIPIGFW>W<AVVTMTTLGYGDMYPQTWSGMLVGALCALA | 460 |
| KCNC3 | IYYAERIGADPDDILGSNHTYFKNIPIGFW>W<AVVTMTTLGYGDMYPKTWSGMLVGALCALA | 526 |
| KCNC4 | IYYAERIGARPSDPRGNDHTDFKNIPIGFW>W<AVVTMTTLGYGDMYPKTWSGMLVGALCALA | 459 |
| KCND1 | MFYAEKGT---------NKTNFTSIPAAFW>Y<TIVTMTTLGYGDMVPSTIAGKIFGSICSLS | 395 |
| KCND2 | MFYAEKGS---------SASKFTSIPAAFW>Y<TIVTMTTLGYGDMVPKTIAGKIFGSICSLS | 393 |
| KCND3 | MFYAEKGS---------SASKFTSIPASFW>Y<TIVTMTTLGYGDMVPKTIAGKIFGSICSLS | 390 |
| KCNF1 | GYTMEQSH---------PETLFKSIPQSFW>W<AIITMTTVGYGDIYPKTTLGKLNAAISFLC | 393 |
| KCNG1 | LYVIENEM-----A---DSPEFTSIPACYW>W<AVITMTTVGYGDMVPRSTPGQVVALSSILS | 447 |
| KCNG2 | VHLAEREL-----G---ARRDFSSVPASYW>W<AVISMTTVGYGDMVPRSLPGQVVALSSILS | 392 |
| KCNG3 | SQLLEHGL-----DLETSNKDFTSIPAACW>W<VIISMTTVGYGDMYPITVPGRILGGVCVVS | 396 |
| KCNG4 | VYVAEKES-----G---RVLEFTSIPASYW>W<AIISMTTVGYGDMVPRSVPGQMVALSSILS | 441 |
| KCNS1 | AYTAEKEE----------DVGFNTIPACWW>W<GTVSMTTVGYGDVVPVTVAGKLAASGCILG | 444 |
| KCNS2 | AYTIEKEE----------NEGLATIPACWW>W<ATVSMTTVGYGDVVPGTTAGKLTASACILA | 397 |
| KCNS3 | IYSVEKDD---------HTSSLTSIPICWW>W<ATISMTTVGYGDTHPVTLAGKLIASTCIIC | 393 |
| KCNV1 | EYFAEQSI---------PDTTFTSVPCAWW>W<ATTSMTTVGYGDIRPDTTTGKIVAFMCILS | 415 |
| KCNV2 | VYSVEHDV---------PSTNFTTIPHSWW>W<AAVSISTVGYGDMYPETHLGRFFAFLCIAF | 480 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.W305R | c.913T>C | Inherited Arrhythmia | LQTS | rs199472741 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | 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.W305S | c.914G>C | Inherited Arrhythmia | LQTS,JLNS | rs120074186 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | JLNS | 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 Arrhythmia | LQTS | 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 Arrhythmia | LQTS | 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 Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538 | |||
| p.W305L | c.914G>T | Inherited Arrhythmia | SIFT: Polyphen: | ||
| Reports | Inherited Arrhythmia | LQTS | 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 | ||