| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ4 | V230E | Hearing loss, non-syndromic, autosomal dominant | High | 9 | 23717403 |
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 | TSAIRGIRFLQILRMLHVDRQGGTWRLLGS>V<VFIHRQELITTLYIGFLGLIFSSYFVYLAE | 284 |
| KCNQ2 | TSALRSLRFLQILRMIRMDRRGGTWKLLGS>V<VYAHSKELVTAWYIGFLCLILASFLVYLAE | 254 |
| KCNQ3 | -TSLRSLRFLQILRMLRMDRRGGTWKLLGS>A<ICAHSKELITAWYIGFLTLILSSFLVYLVE | 283 |
| KCNQ4 | TSALRSMRFLQILRMVRMDRRGGTWKLLGS>V<VYAHSKELITAWYIGFLVLIFASFLVYLAE | 260 |
| KCNQ5 | TSALRSLRFLQILRMVRMDRRGGTWKLLGS>V<VYAHSKELITAWYIGFLVLIFSSFLVYLVE | 288 |
| KCNA1 | LAILRVIRLVRVFRIFKLSRHSKGLQILGQ>T<LKASMRELGLLIFFLFIGVILFSSAVYFAE | 348 |
| KCNA10 | LAILRIIRLVRVFRIFKLSRHSKGLQILGQ>T<LKASMRELGLLIFFLFIGVILFSSAVYFAE | 397 |
| KCNA2 | LAILRVIRLVRVFRIFKLSRHSKGLQILGQ>T<LKASMRELGLLIFFLFIGVILFSSAVYFAE | 350 |
| KCNA3 | LAILRVIRLVRVFRIFKLSRHSKGLQILGQ>T<LKASMRELGLLIFFLFIGVILFSSAVYFAE | 420 |
| KCNA4 | FAILRIIRLVRVFRIFKLSRHSKGLQILGH>T<LRASMRELGLLIFFLFIGVILFSSAVYFAE | 500 |
| KCNA5 | LAILRVIRLVRVFRIFKLSRHSKGLQILGK>T<LQASMRELGLLIFFLFIGVILFSSAVYFAE | 456 |
| KCNA6 | LAILRVIRLVRVFRIFKLSRHSKGLQILGK>T<LQASMRELGLLIFFLFIGVILFSSAVYFAE | 398 |
| KCNA7 | LAILRVIRLVRVFRIFKLSRHSKGLQILGQ>T<LRASMRELGLLIFFLFIGVVLFSSAVYFAE | 334 |
| KCNB1 | RRVVQIFRIMRILRILKLARHSTGLQSLGF>T<LRRSYNELGLLILFLAMGIMIFSSLVFFAE | 353 |
| KCNB2 | RRVVQIFRIMRILRILKLARHSTGLQSLGF>T<LRRSYNELGLLILFLAMGIMIFSSLVFFAE | 357 |
| KCNC1 | LGFLRVVRFVRILRIFKLTRHFVGLRVLGH>T<LRASTNEFLLLIIFLALGVLIFATMIYYAE | 367 |
| KCNC2 | LGFLRVVRFVRILRIFKLTRHFVGLRVLGH>T<LRASTNEFLLLIIFLALGVLIFATMIYYAE | 404 |
| KCNC3 | LGFLRVVRFVRILRIFKLTRHFVGLRVLGH>T<LRASTNEFLLLIIFLALGVLIFATMIYYAE | 470 |
| KCNC4 | LGFLRVVRFVRILRIFKLTRHFVGLRVLGH>T<LRASTNEFLLLIIFLALGVLIFATMIYYAE | 403 |
| KCND1 | SGAFVTLRVFRVFRIFKFSRHSQGLRILGY>T<LKSCASELGFLLFSLTMAIIIFATVMFYAE | 348 |
| KCND2 | SGAFVTLRVFRVFRIFKFSRHSQGLRILGY>T<LKSCASELGFLLFSLTMAIIIFATVMFYAE | 346 |
| KCND3 | SGAFVTLRVFRVFRIFKFSRHSQGLRILGY>T<LKSCASELGFLLFSLTMAIIIFATVMFYAE | 343 |
| KCNF1 | QQAVQALRIMRIARIFKLARHSSGLQTLTY>A<LKRSFKELGLLLMYLAVGIFVFSALGYTME | 346 |
| KCNG1 | GLVLRVLRALRILYVMRLARHSLGLQTLGL>T<ARRCTREFGLLLLFLCVAIALFAPLLYVIE | 399 |
| KCNG2 | GLVLRLLRALRVLYVMRLARHSLGLRSLGL>T<MRRCAREFGLLLLFLCVAMALFAPLVHLAE | 344 |
| KCNG3 | GVTLRVLRMMRIFWVIKLARHFIGLQTLGL>T<LKRCYREMVMLLVFICVAMAIFSALSQLLE | 345 |
| KCNG4 | GLVLRVLRALRILYVMRLARHSLGLQTLGL>T<VRRCTREFGLLLLFLAVAITLFSPLVYVAE | 393 |
| KCNS1 | GKVVQVFRLMRIFRVLKLARHSTGLRSLGA>T<LKHSYREVGILLLYLAVGVSVFSGVAYTAE | 398 |
| KCNS2 | GRVAQVLRLMRIFRILKLARHSTGLRSLGA>T<LKYSYKEVGLLLLYLSVGISIFSVVAYTIE | 351 |
| KCNS3 | GKVVQILRLMRIFRILKLARHSVGLRSLGA>T<LRHSYHEVGLLLLFLSVGISIFSVLIYSVE | 346 |
| KCNV1 | GRIVQVLRLLRALRMLKLGRHSTGLRSLGM>T<ITQCYEEVGLLLLFLSVGISIFSTVEYFAE | 368 |
| KCNV2 | GQVLRVMRLMRIFRILKLARHSTGLRAFGF>T<LRQCYQQVGCLLLFIAMGIFTFSAAVYSVE | 433 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.V254L | c.760G>T | Inherited Arrhythmia | LQTS | rs120074179 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | ||
| Inherited Arrhythmia | LQTS | Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944 | |||
| Inherited Arrhythmia | LQTS | Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538 | |||
| p.V254M | c.760G>A | Inherited Arrhythmia | LQTS | rs120074179 | 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 | KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136 | |||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Mutation analysis in congenital Long QT Syndrome--a case with missense mutations in KCNQ1 and SCN5A. Genet Test. 2003 7(1):57-61. 12820704 | |||
| Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | |||
| Inherited Arrhythmia | LQTS | Effective long-term control of cardiac events with beta-blockers in a family with a common LQT1 mutation. Clin Genet. 2004 65(3):233-41. 14756674 | |||
| Inherited Arrhythmia | LQTS | Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation. 2004 110(15):2119-24. 15466642 | |||
| 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 | Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology. Med Biol Eng Comput. 2006 44(7):543-9. 16937190 | |||
| 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 | Functional effects of mutations in KvLQT1 that cause long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(6):817-26. 10376919 | |||
| Inherited Arrhythmia | LQTS | 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 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 | 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 | 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.V254L | c.760G>C | Inherited Arrhythmia | LQTS | rs120074179 | SIFT: Polyphen: |
| Reports | Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | ||
| Inherited Arrhythmia | LQTS | 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 | |||