| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNA1 | R239S | Episodic ataxia / myokymia | High | 9 | 7842011, 8845167, 9526001 |
| KCNV2 | R320C | Cone dystrophy with supernormal rod ERG | High | 9 | 23725738 |
| KCNQ2 | R144Q | Infantile spasms | High | 9 | 23934111, 25740509 |
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 | ----ALATGT-LF-WMEIVLVVFFGTEYVV>R<LWSAGCRSKYVGLWGRLRFARKPISIIDLI | 204 |
| KCNQ2 | ----KSSEGA-LY-ILEIVTIVVFGVEYFV>R<IWAAGCCCRYRGWRGRLKFARKPFCVIDIM | 174 |
| KCNQ3 | ----TVSGDW-LL-LLETFAIFIFGAEFAL>R<IWAAGCCCRYKGWRGRLKFARKPLCMLDIF | 204 |
| KCNQ4 | ----ELANEC-LL-ILEFVMIVVFGLEYIV>R<VWSAGCCCRYRGWQGRFRFARKPFCVIDFI | 180 |
| KCNQ5 | ----KLASSC-LL-ILEFVMIVVFGLEFII>R<IWSAGCCCRYRGWQGRLRFARKPFCVIDTI | 208 |
| KCNA1 | IYNSNIFTDP-FF-IVETLCIIWFSFELVV>R<---------FFACPSKTDFFKNIMNFIDIV | 260 |
| KCNA10 | VLSQTMFTDP-FF-MVESTCIVWFTFELVL>R<---------FVVCPSKTDFFRNIMNIIDII | 310 |
| KCNA2 | YQQSTSFTDP-FF-IVETLCIIWFSFEFLV>R<---------FFACPSKAGFFTNIMNIIDIV | 261 |
| KCNA3 | RAGASSFSDP-FF-VVETLCIIWFSFELLV>R<---------FFACPSKATFSRNIMNLIDIV | 334 |
| KCNA4 | NSGHTIFNDP-FF-IVETVCIVWFSFEFVV>R<---------CFACPSQALFFKNIMNIIDIV | 410 |
| KCNA5 | PLLPRTLADP-FF-IVETTCVIWFTFELLV>R<---------FFACPSKAGFSRNIMNIIDVV | 363 |
| KCNA6 | TLGGSFFTDP-FF-LVETLCIVWFTFELLV>R<---------FSACPSKPAFFRNIMNIIDLV | 302 |
| KCNA7 | NPPRLPFNDP-FF-VVETLCICWFSFELLV>R<---------LLVCPSKAIFFKNVMNLIDFV | 248 |
| KCNB1 | -----STDNPQLA-HVEAVCIAWFTMEYLL>R<---------FLSSPKKWKFFKGPLNAIDLL | 268 |
| KCNB2 | -----LNDNRQLA-HVEAVCIAWFTMEYLL>R<---------FLSSPNKWKFFKGPLNVIDLL | 272 |
| KCNC1 | RYYREAETEA-FLTYIEGVCVVWFTFEFLM>R<---------VIFCPNKVEFIKNSLNIIDFV | 284 |
| KCNC2 | VLQYEIETDP-ALTYVEGVCVVWFTFEFLV>R<---------IVFSPNKLEFIKNLLNIIDFV | 321 |
| KCNC3 | ITNVEVETEP-FLTYVEGVCVVWFTFEFLM>R<---------ITFCPDKVEFLKSSLNIIDCV | 387 |
| KCNC4 | HFRREVETEP-ILTYIEGVCVLWFTLEFLV>R<---------IVCCPDTLDFVKNLLNIIDFV | 320 |
| KCND1 | QPCGERFPQA-FF-CMDTACVLIFTGEYLL>R<---------LFAAPSRCRFLRSVMSLIDVV | 270 |
| KCND2 | LPCGERYAVA-FF-CLDTACVMIFTVEYLL>R<---------LAAAPSRYRFVRSVMSIIDVV | 268 |
| KCND3 | LPCGERYSVA-FF-CLDTACVMIFTVEYLL>R<---------LFAAPSRYRFIRSVMSIIDVV | 265 |
| KCNF1 | -----RVEHPTLE-NVETACIGWFTLEYLL>R<---------LFSSPNKLHFALSFMNIVDVL | 261 |
| KCNG1 | ----SQMCHN-VF-IVESVCVGWFSLEFLL>R<---------LIQAPSKFAFLRSPLTLIDLV | 307 |
| KCNG2 | ----SPKCRS-LF-VLETVCVAWFSFEFLL>R<---------SLQAESKCAFLRAPLNIIDIL | 257 |
| KCNG3 | RYSAGPGREP-SG-IIEAICIGWFTAECIV>R<---------FIVSKNKCEFVKRPLNIIDLL | 260 |
| KCNG4 | ----SRKCYY-IF-IVETICVAWFSLEFCL>R<---------FVQAQDKCQFFQGPLNIIDIL | 301 |
| KCNS1 | RSPEGVRDDPVLR-RLEYFCIAWFSFEVSS>R<---------LLLAPSTRNFFCHPLNLIDIV | 311 |
| KCNS2 | -----PGEDPRFE-IVEHFGIAWFTFELVA>R<---------FAVAPDFLKFFKNALNLIDLM | 266 |
| KCNS3 | ------VDDPVLE-GVEIACIAWFTGELAV>R<---------LAAAPCQKKFWKNPLNIIDFV | 261 |
| KCNV1 | -----WLDLQLLE-ILEYVCISWFTGEFVL>R<---------FLCVRDRCRFLRKVPNIIDLL | 281 |
| KCNV2 | ----GPDLRPILE-HVEMLCMGFFTLEYLL>R<---------LASTPDLRRFARSALNLVDLV | 341 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R174C | c.520C>T | Inherited Arrhythmia | LQTS,JLNS | rs199472696 | 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 | Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Hum Mutat. 2001 18(5):451-7. 11668638 | |||
| 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 | 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 | JLNS | Prevalence and potential genetic determinants of sensorineural deafness in KCNQ1 homozygosity and compound heterozygosity. Circ Cardiovasc Genet. 2013 6(2):193-200. doi: 10.1161/CIRCGENETICS.112.964684 23392653 | |||
| Inherited Arrhythmia | LQTS | Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 16(17):5472-9. 9312006 | |||
| p.R174H | c.521G>A | Inherited Arrhythmia | LQTS | rs199472697 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | [Congenital long QT syndrome. The value of genetics in prognostic evaluation]. Arch Mal Coeur Vaiss. 1999 92(5):557-63. 10367071 | ||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| 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 | 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 | 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 | |||
| p.R174P | c.521G>C | Inherited Arrhythmia | LQTS | rs199472697 | 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 | ||
| p.R174L | c.521G>T | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome. Circ Arrhythm Electrophysiol. 2011 4(6):867-73. 21956039 | ||