| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ2 | R213W | Epilepsy, benign neonatal | High | 9 | 18353052, 22455920, 23440208 |
| KCNA1 | R307C | Episodic ataxia 1 | High | 9 | 20660867 |
| KCNQ2 | R213Q | Epileptic encephalopathy, neonatal | High | 9 | 22275249, 22455920, 23440208, 24318194, 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 | ----SKGQVFATSAIRGIRFLQILRMLHVD>R<QGGTWRLLGSVVFIHRQELITTLYIGFLGL | 273 |
| KCNQ2 | ----SQGNVFATSALRSLRFLQILRMIRMD>R<RGGTWKLLGSVVYAHSKELVTAWYIGFLCL | 243 |
| KCNQ3 | ----NQGNVLA-TSLRSLRFLQILRMLRMD>R<RGGTWKLLGSAICAHSKELITAWYIGFLTL | 272 |
| KCNQ4 | ----TQGNIFATSALRSMRFLQILRMVRMD>R<RGGTWKLLGSVVYAHSKELITAWYIGFLVL | 249 |
| KCNQ5 | ----TQGNIFATSALRSLRFLQILRMVRMD>R<RGGTWKLLGSVVYAHSKELITAWYIGFLVL | 277 |
| KCNA1 | -N-QKGEQATSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGQTLKASMRELGLLIFFLFIGV | 337 |
| KCNA10 | ----SAQQNMSLAILRIIRLVRVFRIFKLS>R<HSKGLQILGQTLKASMRELGLLIFFLFIGV | 386 |
| KCNA2 | -DAQQGQQAMSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGQTLKASMRELGLLIFFLFIGV | 339 |
| KCNA3 | ---GNGQQAMSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGQTLKASMRELGLLIFFLFIGV | 409 |
| KCNA4 | -GNGQQQQAMSFAILRIIRLVRVFRIFKLS>R<HSKGLQILGHTLRASMRELGLLIFFLFIGV | 489 |
| KCNA5 | GGGQNGQQAMSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGKTLQASMRELGLLIFFLFIGV | 445 |
| KCNA6 | GGGQNGQQAMSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGKTLQASMRELGLLIFFLFIGV | 387 |
| KCNA7 | ---GVGQQAMSLAILRVIRLVRVFRIFKLS>R<HSKGLQILGQTLRASMRELGLLIFFLFIGV | 323 |
| KCNB1 | --KSVLQFQNVRRVVQIFRIMRILRILKLA>R<HSTGLQSLGFTLRRSYNELGLLILFLAMGI | 342 |
| KCNB2 | --KSVLQFQNVRRVVQIFRIMRILRILKLA>R<HSTGLQSLGFTLRRSYNELGLLILFLAMGI | 346 |
| KCNC1 | --LSSKAAKDVLGFLRVVRFVRILRIFKLT>R<HFVGLRVLGHTLRASTNEFLLLIIFLALGV | 356 |
| KCNC2 | --LSSKAAKDVLGFLRVVRFVRILRIFKLT>R<HFVGLRVLGHTLRASTNEFLLLIIFLALGV | 393 |
| KCNC3 | --LSSKAAKDVLGFLRVVRFVRILRIFKLT>R<HFVGLRVLGHTLRASTNEFLLLIIFLALGV | 459 |
| KCNC4 | --LSSKAARDVLGFLRVVRFVRILRIFKLT>R<HFVGLRVLGHTLRASTNEFLLLIIFLALGV | 392 |
| KCND1 | ------KNDDVSGAFVTLRVFRVFRIFKFS>R<HSQGLRILGYTLKSCASELGFLLFSLTMAI | 337 |
| KCND2 | ------DNEDVSGAFVTLRVFRVFRIFKFS>R<HSQGLRILGYTLKSCASELGFLLFSLTMAI | 335 |
| KCND3 | ------NNEDVSGAFVTLRVFRVFRIFKFS>R<HSQGLRILGYTLKSCASELGFLLFSLTMAI | 332 |
| KCNF1 | -GARMMELTNVQQAVQALRIMRIARIFKLA>R<HSSGLQTLTYALKRSFKELGLLLMYLAVGI | 335 |
| KCNG1 | PGAGNSYLDKVGLVLRVLRALRILYVMRLA>R<HSLGLQTLGLTARRCTREFGLLLLFLCVAI | 388 |
| KCNG2 | GPGGTKLLERAGLVLRLLRALRVLYVMRLA>R<HSLGLRSLGLTMRRCAREFGLLLLFLCVAM | 333 |
| KCNG3 | FTGENSQLQRAGVTLRVLRMMRIFWVIKLA>R<HFIGLQTLGLTLKRCYREMVMLLVFICVAM | 334 |
| KCNG4 | RPSGSSYLEKVGLVLRVLRALRILYVMRLA>R<HSLGLQTLGLTVRRCTREFGLLLLFLAVAI | 382 |
| KCNS1 | --QGGKEFGHLGKVVQVFRLMRIFRVLKLA>R<HSTGLRSLGATLKHSYREVGILLLYLAVGV | 387 |
| KCNS2 | --ESTPTLANLGRVAQVLRLMRIFRILKLA>R<HSTGLRSLGATLKYSYKEVGLLLLYLSVGI | 340 |
| KCNS3 | --EESEDIENMGKVVQILRLMRIFRILKLA>R<HSVGLRSLGATLRHSYHEVGLLLLFLSVGI | 335 |
| KCNV1 | --QTTQELENVGRIVQVLRLLRALRMLKLG>R<HSTGLRSLGMTITQCYEEVGLLLLFLSVGI | 357 |
| KCNV2 | RGQTVGSVGKVGQVLRVMRLMRIFRILKLA>R<HSTGLRAFGFTLRQCYQQVGCLLLFIAMGI | 422 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R243C | c.727C>T | Inherited Arrhythmia | LQTS | rs199472713 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697 | |||
| 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 | Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 15(2):190-9. 15028050 | |||
| 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 | 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 | PKA and PKC partially rescue long QT type 1 phenotype by restoring channel-PIP2 interactions. Channels (Austin). 2010 4(1):3-11. 19934648 | |||
| 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 | |||
| Inherited Arrhythmia | LQTS | Posthumous diagnosis of long QT syndrome from neonatal screening cards. Heart Rhythm. 2010 7(4):481-6. 20167303 | |||
| Inherited Arrhythmia | LQTS | RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science. 2015 347(6218):1254806. doi: 10.1126/science.1254806. 25525159 | |||
| p.R243H | c.728G>A | Inherited Arrhythmia | LQTS,JLNS | rs120074196 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred. Hum Mutat. 1998 11(2):158-65. 9482580 | ||
| Inherited Arrhythmia | JLNS | Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias. Am J Hum Genet. 1999 64(4):1015-23. 10090886 | |||
| 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 | Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 15(2):190-9. 15028050 | |||
| Inherited Arrhythmia | JLNS | Kv7.1 (KCNQ1) properties and channelopathies. J Physiol. 2008 586(7):1785-9. 18174212 | |||
| Inherited Arrhythmia | JLNS | Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. Circ Arrhythm Electrophysiol. 2009 2(5):511-23. 19843919 | |||
| Inherited Arrhythmia | JLNS | Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk. Cardiovasc Res. 2000 45(4):971-80. 10728423 | |||
| 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 | Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc Res. 2005 67(3):476-86. 15935335 | |||
| 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 | Impaired KCNQ1-KCNE1 and phosphatidylinositol-4,5-bisphosphate interaction underlies the long QT syndrome. Circ Res. 2005 96(7):730-9. 15746441 | |||
| Inherited Arrhythmia | JLNS | A long QT mutation substitutes cholesterol for phosphatidylinositol-4,5-bisphosphate in KCNQ1 channel regulation. PLoS One. 2014 9(3):e93255. doi: 10.1371/journal.pone.0093255. eC 24681627 | |||
| Inherited Arrhythmia | JLNS | Jervell and Lange-Nielsen syndrome: homozygous missense mutation of KCNQ1 in a Turkish family. Pediatr Cardiol. 2013 34(8):2063-7. doi: 10.1007/s00246-013-0634-3. 23400408 | |||
| Inherited Arrhythmia | JLNS | Jervell and Lange-Nielsen syndrome with homozygous missense mutation of the KCNQ1 gene. Turk J Pediatr. 2014 56(5):542-5. 26022593 | |||
| p.R243P | c.728G>C | Inherited Arrhythmia | LQTS | rs120074196 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724 | ||
| p.R243S | c.727C>A | Inherited Arrhythmia | LQTS | rs199472713 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome. J Cardiovasc Electrophysiol. 2009 20(8):859-65. 19490272 | ||