| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNA1 | E325D | Episodic ataxia / myokymia | High | 9 | 8541859, 21307345, 8845167, 9526001 |
| KCNQ2 | E231D | Epileptic encephalopathy, neonatal | High | 9 | 26795593 |
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 | RFLQILRMLHVDRQGGTWRLLGSVVFIHRQ>E<LITTLYIGFLGLIFSSYFVYLAEKDAVN-- | 289 |
| KCNQ2 | RFLQILRMIRMDRRGGTWKLLGSVVYAHSK>E<LVTAWYIGFLCLILASFLVYLAEKGE---- | 257 |
| KCNQ3 | RFLQILRMLRMDRRGGTWKLLGSAICAHSK>E<LITAWYIGFLTLILSSFLVYLVEKDVPEVD | 290 |
| KCNQ4 | RFLQILRMVRMDRRGGTWKLLGSVVYAHSK>E<LITAWYIGFLVLIFASFLVYLAEKDA---- | 263 |
| KCNQ5 | RFLQILRMVRMDRRGGTWKLLGSVVYAHSK>E<LITAWYIGFLVLIFSSFLVYLVEKDA---- | 291 |
| KCNA1 | RLVRVFRIFKLSRHSKGLQILGQTLKASMR>E<LGLLIFFLFIGVILFSSAVYFAEAEE---- | 351 |
| KCNA10 | RLVRVFRIFKLSRHSKGLQILGQTLKASMR>E<LGLLIFFLFIGVILFSSAVYFAEVDE---- | 400 |
| KCNA2 | RLVRVFRIFKLSRHSKGLQILGQTLKASMR>E<LGLLIFFLFIGVILFSSAVYFAEADE---- | 353 |
| KCNA3 | RLVRVFRIFKLSRHSKGLQILGQTLKASMR>E<LGLLIFFLFIGVILFSSAVYFAEADD---- | 423 |
| KCNA4 | RLVRVFRIFKLSRHSKGLQILGHTLRASMR>E<LGLLIFFLFIGVILFSSAVYFAEADE---- | 503 |
| KCNA5 | RLVRVFRIFKLSRHSKGLQILGKTLQASMR>E<LGLLIFFLFIGVILFSSAVYFAEADN---- | 459 |
| KCNA6 | RLVRVFRIFKLSRHSKGLQILGKTLQASMR>E<LGLLIFFLFIGVILFSSAVYFAEADD---- | 401 |
| KCNA7 | RLVRVFRIFKLSRHSKGLQILGQTLRASMR>E<LGLLIFFLFIGVVLFSSAVYFAEVDR---- | 337 |
| KCNB1 | RIMRILRILKLARHSTGLQSLGFTLRRSYN>E<LGLLILFLAMGIMIFSSLVFFAEKDE---- | 356 |
| KCNB2 | RIMRILRILKLARHSTGLQSLGFTLRRSYN>E<LGLLILFLAMGIMIFSSLVFFAEKDE---- | 360 |
| KCNC1 | RFVRILRIFKLTRHFVGLRVLGHTLRASTN>E<FLLLIIFLALGVLIFATMIYYAERIGAQPN | 374 |
| KCNC2 | RFVRILRIFKLTRHFVGLRVLGHTLRASTN>E<FLLLIIFLALGVLIFATMIYYAERVGAQPN | 411 |
| KCNC3 | RFVRILRIFKLTRHFVGLRVLGHTLRASTN>E<FLLLIIFLALGVLIFATMIYYAERIGADPD | 477 |
| KCNC4 | RFVRILRIFKLTRHFVGLRVLGHTLRASTN>E<FLLLIIFLALGVLIFATMIYYAERIGARPS | 410 |
| KCND1 | RVFRVFRIFKFSRHSQGLRILGYTLKSCAS>E<LGFLLFSLTMAIIIFATVMFYAEKGT---- | 351 |
| KCND2 | RVFRVFRIFKFSRHSQGLRILGYTLKSCAS>E<LGFLLFSLTMAIIIFATVMFYAEKGS---- | 349 |
| KCND3 | RVFRVFRIFKFSRHSQGLRILGYTLKSCAS>E<LGFLLFSLTMAIIIFATVMFYAEKGS---- | 346 |
| KCNF1 | RIMRIARIFKLARHSSGLQTLTYALKRSFK>E<LGLLLMYLAVGIFVFSALGYTMEQSH---- | 349 |
| KCNG1 | RALRILYVMRLARHSLGLQTLGLTARRCTR>E<FGLLLLFLCVAIALFAPLLYVIENEM---- | 402 |
| KCNG2 | RALRVLYVMRLARHSLGLRSLGLTMRRCAR>E<FGLLLLFLCVAMALFAPLVHLAEREL---- | 347 |
| KCNG3 | RMMRIFWVIKLARHFIGLQTLGLTLKRCYR>E<MVMLLVFICVAMAIFSALSQLLEHGL---- | 348 |
| KCNG4 | RALRILYVMRLARHSLGLQTLGLTVRRCTR>E<FGLLLLFLAVAITLFSPLVYVAEKES---- | 396 |
| KCNS1 | RLMRIFRVLKLARHSTGLRSLGATLKHSYR>E<VGILLLYLAVGVSVFSGVAYTAEKEE---- | 401 |
| KCNS2 | RLMRIFRILKLARHSTGLRSLGATLKYSYK>E<VGLLLLYLSVGISIFSVVAYTIEKEE---- | 354 |
| KCNS3 | RLMRIFRILKLARHSVGLRSLGATLRHSYH>E<VGLLLLFLSVGISIFSVLIYSVEKDD---- | 349 |
| KCNV1 | RLLRALRMLKLGRHSTGLRSLGMTITQCYE>E<VGLLLLFLSVGISIFSTVEYFAEQSI---- | 371 |
| KCNV2 | RLMRIFRILKLARHSTGLRAFGFTLRQCYQ>Q<VGCLLLFIAMGIFTFSAAVYSVEHDV---- | 436 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.E261D | c.783G>C | Inherited Arrhythmia | LQTS,JLNS | rs199472721 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | JLNS | Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet. 1999 89(3):137-46. 10704188 | ||
| Inherited Arrhythmia | JLNS | A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome. Cardiovasc Res. 2001 51(4):670-80. 11530100 | |||
| 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 | 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 Arrhythmia | LQTS | Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen. Hum Genet. 2000 107(5):499-503. 11140949 | |||
| Inherited Arrhythmia | LQTS | Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538 | |||
| Inherited Arrhythmia | LQTS | Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc Res. 2005 67(3):476-86. 15935335 | |||
| Inherited Arrhythmia | LQTS | Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. Genet Test Mol Biomarkers. 2013 17(7):553-61. doi: 10.1089/gtmb.2012.0118. 23631430 | |||
| p.E261K | c.781G>A | Inherited Arrhythmia | LQTS | rs199472722 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136 | ||
| Inherited Arrhythmia | LQTS | Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits. J Biol Chem. 1999 274(30):21063-70. 10409658 | |||
| Inherited Arrhythmia | LQTS | Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc Res. 2005 67(3):476-86. 15935335 | |||
| p.E261Q | c.781G>C | Inherited Arrhythmia | LQTS | rs199472722 | 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 | ||
| p.E261V | c.782A>T | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Genetic characteristics of children and adolescents with long-QT syndrome diagnosed by school-based electrocardiographic screening programs. Circ Arrhythm Electrophysiol. 2014 7(1):107-12. doi: 10.1161/CIRCEP.113.000426. 24363352 | ||
| p.E261G | c.782A>G | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction. Eur J Hum Genet. 2016 24(8):1160-6. doi: 10.1038/ejhg.2015.257. 26669661 | ||