| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ2 | G159E | Seizures, benign neonatal | High | 8 | 23360469 |
| KCNQ2 | G159R | Epilepsy, benign neonatal | High | 8 | 25982755 |
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 | MEIVLVVFFGTEYVVRLWSAGCRSKYVGLW>G<RLRFARKPISIIDLIVVVASMVVLCVG--- | 216 |
| KCNQ2 | LEIVTIVVFGVEYFVRIWAAGCCCRYRGWR>G<RLKFARKPFCVIDIMVLIASIAVLAAG--- | 186 |
| KCNQ3 | LETFAIFIFGAEFALRIWAAGCCCRYKGWR>G<RLKFARKPLCMLDIFVLIASVPVVAVG--- | 216 |
| KCNQ4 | LEFVMIVVFGLEYIVRVWSAGCCCRYRGWQ>G<RFRFARKPFCVIDFIVFVASVAVIAAG--- | 192 |
| KCNQ5 | LEFVMIVVFGLEFIIRIWSAGCCCRYRGWQ>G<RLRFARKPFCVIDTIVLIASIAVVSAK--- | 220 |
| KCNA1 | VETLCIIWFSFELVVR---------FFACP>S<KTDFFKNIMNFIDIVAIIPYFITLGTEIAE | 275 |
| KCNA10 | VESTCIVWFTFELVLR---------FVVCP>S<KTDFFRNIMNIIDIISIIPYFATLITELVQ | 325 |
| KCNA2 | VETLCIIWFSFEFLVR---------FFACP>S<KAGFFTNIMNIIDIVAIIPYFITLGTELAE | 276 |
| KCNA3 | VETLCIIWFSFELLVR---------FFACP>S<KATFSRNIMNLIDIVAIIPYFITLGTELAE | 349 |
| KCNA4 | VETVCIVWFSFEFVVR---------CFACP>S<QALFFKNIMNIIDIVSILPYFITLGTDLAQ | 425 |
| KCNA5 | VETTCVIWFTFELLVR---------FFACP>S<KAGFSRNIMNIIDVVAIFPYFITLGTELAE | 378 |
| KCNA6 | VETLCIVWFTFELLVR---------FSACP>S<KPAFFRNIMNIIDLVAIFPYFITLGTELVQ | 317 |
| KCNA7 | VETLCICWFSFELLVR---------LLVCP>S<KAIFFKNVMNLIDFVAILPYFVALGTELAR | 263 |
| KCNB1 | VEAVCIAWFTMEYLLR---------FLSSP>K<KWKFFKGPLNAIDLLAILPYYVTIFLTES- | 282 |
| KCNB2 | VEAVCIAWFTMEYLLR---------FLSSP>N<KWKFFKGPLNVIDLLAILPYYVTIFLTES- | 286 |
| KCNC1 | IEGVCVVWFTFEFLMR---------VIFCP>N<KVEFIKNSLNIIDFVAILPFYLEVGLSG-- | 297 |
| KCNC2 | VEGVCVVWFTFEFLVR---------IVFSP>N<KLEFIKNLLNIIDFVAILPFYLEVGLSG-- | 334 |
| KCNC3 | VEGVCVVWFTFEFLMR---------ITFCP>D<KVEFLKSSLNIIDCVAILPFYLEVGLSG-- | 400 |
| KCNC4 | IEGVCVLWFTLEFLVR---------IVCCP>D<TLDFVKNLLNIIDFVAILPFYLEVGLSG-- | 333 |
| KCND1 | MDTACVLIFTGEYLLR---------LFAAP>S<RCRFLRSVMSLIDVVAILPYYIGLLVP--- | 282 |
| KCND2 | LDTACVMIFTVEYLLR---------LAAAP>S<RYRFVRSVMSIIDVVAILPYYIGLVMT--- | 280 |
| KCND3 | LDTACVMIFTVEYLLR---------LFAAP>S<RYRFIRSVMSIIDVVAIMPYYIGLVMT--- | 277 |
| KCNF1 | VETACIGWFTLEYLLR---------LFSSP>N<KLHFALSFMNIVDVLAILPFYVSLTLTHL- | 275 |
| KCNG1 | VESVCVGWFSLEFLLR---------LIQAP>S<KFAFLRSPLTLIDLVAILPYYITLLVDGAA | 322 |
| KCNG2 | LETVCVAWFSFEFLLR---------SLQAE>S<KCAFLRAPLNIIDILALLPFYVSLLLGL-- | 270 |
| KCNG3 | IEAICIGWFTAECIVR---------FIVSK>N<KCEFVKRPLNIIDLLAITPYYISVLMTV-- | 273 |
| KCNG4 | VETICVAWFSLEFCLR---------FVQAQ>D<KCQFFQGPLNIIDILAISPYYVSLAVSEEP | 316 |
| KCNS1 | LEYFCIAWFSFEVSSR---------LLLAP>S<TRNFFCHPLNLIDIVSVLPFYLTLLAGVAL | 326 |
| KCNS2 | VEHFGIAWFTFELVAR---------FAVAP>D<FLKFFKNALNLIDLMSIVPFYITLVVNLV- | 280 |
| KCNS3 | VEIACIAWFTGELAVR---------LAAAP>C<QKKFWKNPLNIIDFVSIIPFYATLAVDTK- | 275 |
| KCNV1 | LEYVCISWFTGEFVLR---------FLCVR>D<RCRFLRKVPNIIDLLAILPFYITLLVESLS | 296 |
| KCNV2 | VEMLCMGFFTLEYLLR---------LASTP>D<LRRFARSALNLVDLVAILPLYLQLLLECFT | 356 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.G189E | c.566G>A | Inherited Arrhythmia | LQTS | rs199473400 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | 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 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.G189R | c.565G>C | Inherited Arrhythmia | LQTS | rs104894252 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144 | ||
| Inherited Arrhythmia | LQTS | Functional effects of mutations in KvLQT1 that cause long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(6):817-26. 10376919 | |||
| Inherited Arrhythmia | LQTS | Mortality of inherited arrhythmia syndromes: insight into their natural history. Circ Cardiovasc Genet. 2012 5(2):183-9. 22373669 | |||
| Inherited Arrhythmia | LQTS | Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation. 2012 125(16):1988-96. 22456477 | |||
| Inherited Arrhythmia | LQTS | Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244 | |||
| p.G189R | c.565G>A | Inherited Arrhythmia | LQTS | rs104894252 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244 | ||
| Inherited Arrhythmia | LQTS | Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144 | |||
| Inherited Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144 | |||