| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ3 | R230C | Intellectual disability, nonsyndromic | High | 9 | 23020937, 23934111, 25740509, 26350515 |
| KCNQ2 | R201H | Epileptic encephalopathy, early onset | High | 9 | 23708187, 25740509 |
| KCNQ2 | R201C | Epileptic encephalopathy, neonatal | High | 9 | 24107868, 25740509 |
| KCNA2 | R297Q | Ataxia & myoclonic epilepsy | High | 9 | 25477152, 25751627 |
| KCNQ3 | R230S | Intellectual disability | High | 9 | 26350204 |
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 | ----------------SKGQVFATSAIRGI>R<FLQILRMLHVDRQGGTWRLLGSVVFIHRQE | 261 |
| KCNQ2 | ----------------SQGNVFATSALRSL>R<FLQILRMIRMDRRGGTWKLLGSVVYAHSKE | 231 |
| KCNQ3 | ----------------NQGNVLA-TSLRSL>R<FLQILRMLRMDRRGGTWKLLGSAICAHSKE | 260 |
| KCNQ4 | ----------------TQGNIFATSALRSM>R<FLQILRMVRMDRRGGTWKLLGSVVYAHSKE | 237 |
| KCNQ5 | ----------------TQGNIFATSALRSL>R<FLQILRMVRMDRRGGTWKLLGSVVYAHSKE | 265 |
| KCNA1 | IAEQEG-------N-QKGEQATSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGQTLKASMRE | 325 |
| KCNA10 | LVQETEP---------SAQQNMSLAILRII>R<LVRVFRIFKLSRHSKGLQILGQTLKASMRE | 374 |
| KCNA2 | LAEKPE-------DAQQGQQAMSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGQTLKASMRE | 327 |
| KCNA3 | LAERQ----------GNGQQAMSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGQTLKASMRE | 397 |
| KCNA4 | LAQQQGG------GNGQQQQAMSFAILRII>R<LVRVFRIFKLSRHSKGLQILGHTLRASMRE | 477 |
| KCNA5 | LAEQQ---PGGGGGGQNGQQAMSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGKTLQASMRE | 433 |
| KCNA6 | LVQQQEQQPASGGGGQNGQQAMSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGKTLQASMRE | 375 |
| KCNA7 | LARQR----------GVGQQAMSLAILRVI>R<LVRVFRIFKLSRHSKGLQILGQTLRASMRE | 311 |
| KCNB1 | ES---N--------KSVLQFQNVRRVVQIF>R<IMRILRILKLARHSTGLQSLGFTLRRSYNE | 330 |
| KCNB2 | ES---N--------KSVLQFQNVRRVVQIF>R<IMRILRILKLARHSTGLQSLGFTLRRSYNE | 334 |
| KCNC1 | G-------------LSSKAAKDVLGFLRVV>R<FVRILRIFKLTRHFVGLRVLGHTLRASTNE | 344 |
| KCNC2 | G-------------LSSKAAKDVLGFLRVV>R<FVRILRIFKLTRHFVGLRVLGHTLRASTNE | 381 |
| KCNC3 | G-------------LSSKAAKDVLGFLRVV>R<FVRILRIFKLTRHFVGLRVLGHTLRASTNE | 447 |
| KCNC4 | G-------------LSSKAARDVLGFLRVV>R<FVRILRIFKLTRHFVGLRVLGHTLRASTNE | 380 |
| KCND1 | ------------------KNDDVSGAFVTL>R<VFRVFRIFKFSRHSQGLRILGYTLKSCASE | 325 |
| KCND2 | ------------------DNEDVSGAFVTL>R<VFRVFRIFKFSRHSQGLRILGYTLKSCASE | 323 |
| KCND3 | ------------------NNEDVSGAFVTL>R<VFRVFRIFKFSRHSQGLRILGYTLKSCASE | 320 |
| KCNF1 | HL-----------GARMMELTNVQQAVQAL>R<IMRIARIFKLARHSSGLQTLTYALKRSFKE | 323 |
| KCNG1 | GAAAGRR----KPGAGNSYLDKVGLVLRVL>R<ALRILYVMRLARHSLGLQTLGLTARRCTRE | 376 |
| KCNG2 | L-----A----AGPGGTKLLERAGLVLRLL>R<ALRVLYVMRLARHSLGLRSLGLTMRRCARE | 321 |
| KCNG3 | V-----------FTGENSQLQRAGVTLRVL>R<MMRIFWVIKLARHFIGLQTLGLTLKRCYRE | 322 |
| KCNG4 | EEPPEDG----ERPSGSSYLEKVGLVLRVL>R<ALRILYVMRLARHSLGLQTLGLTVRRCTRE | 370 |
| KCNS1 | VALG-D--------QGGKEFGHLGKVVQVF>R<LMRIFRVLKLARHSTGLRSLGATLKHSYRE | 375 |
| KCNS2 | LV---V--------ESTPTLANLGRVAQVL>R<LMRIFRILKLARHSTGLRSLGATLKYSYKE | 328 |
| KCNS3 | TK---E--------EESEDIENMGKVVQIL>R<LMRIFRILKLARHSVGLRSLGATLRHSYHE | 323 |
| KCNV1 | SLSG-S--------QTTQELENVGRIVQVL>R<LLRALRMLKLGRHSTGLRSLGMTITQCYEE | 345 |
| KCNV2 | CFTGEGH----QRGQTVGSVGKVGQVLRVM>R<LMRIFRILKLARHSTGLRAFGFTLRQCYQQ | 410 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R231C | c.691C>T | Inherited Arrhythmia | LQTS,AF | rs199473457 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | [Congenital long QT syndrome in newborns]. Arch Pediatr. 2002 9(8):805-9. 12205790 | ||
| Other Cardiac Phenotype | Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol. 2004 43(5):826-30. 14998624 | ||||
| Inherited Arrhythmia | LQTS | Four potassium channel mutations account for 73% of the genetic spectrum underlying long-QT syndrome (LQTS) and provide evidence for a strong founder effect in Finland. Ann Med. 2004 36 Suppl 1:53-63. 15176425 | |||
| 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 | |||
| 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 | Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. Circ Arrhythm Electrophysiol. 2009 2(5):511-23. 19843919 | |||
| Inherited Arrhythmia | AF | R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation. Heart Rhythm. 2011 8(1):48-55. 20850564 | |||
| Inherited Arrhythmia | LQTS | Overlapping cardiac phenotype associated with a familial mutation in the voltage sensor of the KCNQ1 channel. Cell Physiol Biochem. 2012 29(5-6):809-18. 22613981 | |||
| Inherited Arrhythmia | LQTS | Atrial Fibrillation and Long QT Syndrome Presenting in a 12-Year-Old Girl. Case Rep Pediatr. 2012 2012:124838. doi: 10.1155/2012/124838. 23193492 | |||
| p.R231H | c.692G>A | Inherited Arrhythmia | LQTS,AF | rs199472709 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | 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 | AF | A KCNQ1 mutation causes a high penetrance for familial atrial fibrillation. J Cardiovasc Electrophysiol. 2013 24(5):562-9. doi: 10.1111/jce.12068. 23350853 | |||
| p.Arg231Ser | c.691C>A | Unknown | SIFT: Polyphen: | ||