| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ4 | L281S | Deafness, autosomal dominant 2 | Medium | 9 | 10571947, 20966080, 23750663 |
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 | KDAVN-----ESGRVEFGSYADALWWGVVT>V<TTIGYGDKVPQTWVGKTIASCFSVFAISFF | 340 |
| KCNQ2 | KGE----------NDHFDTYADALWWGLIT>L<TTIGYGDKYPQTWNGRLLAATFTLIGVSFF | 305 |
| KCNQ3 | KDVPEVDAQGEEMKEEFETYADALWWGLIT>L<ATIGYGDKTPKTWEGRLIAATFSLIGVSFF | 344 |
| KCNQ4 | KDA----------NSDFSSYADSLWWGTIT>L<TTIGYGDKTPHTWLGRVLAAGFALLGISFF | 311 |
| KCNQ5 | KDA----------NKEFSTYADALWWGTIT>L<TTIGYGDKTPLTWLGRLLSAGFALLGISFF | 339 |
| KCNA1 | AEE---------AESHFSSIPDAFWWAVVS>M<TTVGYGDMYPVTIGGKIVGSLCAIAGVLTI | 400 |
| KCNA10 | VDE---------PESHFSSIPDGFWWAVVT>M<TTVGYGDMCPTTPGGKIVGTLCAIAGVLTI | 449 |
| KCNA2 | ADE---------RESQFPSIPDAFWWAVVS>M<TTVGYGDMVPTTIGGKIVGSLCAIAGVLTI | 402 |
| KCNA3 | ADD---------PTSGFSSIPDAFWWAVVT>M<TTVGYGDMHPVTIGGKIVGSLCAIAGVLTI | 472 |
| KCNA4 | ADE---------PTTHFQSIPDAFWWAVVT>M<TTVGYGDMKPITVGGKIVGSLCAIAGVLTI | 552 |
| KCNA5 | ADN---------QGTHFSSIPDAFWWAVVT>M<TTVGYGDMRPITVGGKIVGSLCAIAGVLTI | 508 |
| KCNA6 | ADD---------DDSLFPSIPDAFWWAVVT>M<TTVGYGDMYPMTVGGKIVGSLCAIAGVLTI | 450 |
| KCNA7 | VDR---------VDSHFTSIPESFWWAVVT>M<TTVGYGDMAPVTVGGKIVGSLCAIAGVLTI | 386 |
| KCNB1 | KDE---------DDTKFKSIPASFWWATIT>M<TTVGYGDIYPKTLLGKIVGGLCCIAGVLVI | 405 |
| KCNB2 | KDE---------DATKFTSIPASFWWATIT>M<TTVGYGDIYPKTLLGKIVGGLCCIAGVLVI | 409 |
| KCNC1 | RIGAQPNDPSASEHTHFKNIPIGFWWAVVT>M<TTLGYGDMYPQTWSGMLVGALCALAGVLTI | 428 |
| KCNC2 | RVGAQPNDPSASEHTQFKNIPIGFWWAVVT>M<TTLGYGDMYPQTWSGMLVGALCALAGVLTI | 465 |
| KCNC3 | RIGADPDDILGSNHTYFKNIPIGFWWAVVT>M<TTLGYGDMYPKTWSGMLVGALCALAGVLTI | 531 |
| KCNC4 | RIGARPSDPRGNDHTDFKNIPIGFWWAVVT>M<TTLGYGDMYPKTWSGMLVGALCALAGVLTI | 464 |
| KCND1 | KGT---------NKTNFTSIPAAFWYTIVT>M<TTLGYGDMVPSTIAGKIFGSICSLSGVLVI | 400 |
| KCND2 | KGS---------SASKFTSIPAAFWYTIVT>M<TTLGYGDMVPKTIAGKIFGSICSLSGVLVI | 398 |
| KCND3 | KGS---------SASKFTSIPASFWYTIVT>M<TTLGYGDMVPKTIAGKIFGSICSLSGVLVI | 395 |
| KCNF1 | QSH---------PETLFKSIPQSFWWAIIT>M<TTVGYGDIYPKTTLGKLNAAISFLCGVIAI | 398 |
| KCNG1 | NEM-----A---DSPEFTSIPACYWWAVIT>M<TTVGYGDMVPRSTPGQVVALSSILSGILLM | 452 |
| KCNG2 | REL-----G---ARRDFSSVPASYWWAVIS>M<TTVGYGDMVPRSLPGQVVALSSILSGILLM | 397 |
| KCNG3 | HGL-----DLETSNKDFTSIPAACWWVIIS>M<TTVGYGDMYPITVPGRILGGVCVVSGIVLL | 401 |
| KCNG4 | KES-----G---RVLEFTSIPASYWWAIIS>M<TTVGYGDMVPRSVPGQMVALSSILSGILIM | 446 |
| KCNS1 | KEE----------DVGFNTIPACWWWGTVS>M<TTVGYGDVVPVTVAGKLAASGCILGGILVV | 449 |
| KCNS2 | KEE----------NEGLATIPACWWWATVS>M<TTVGYGDVVPGTTAGKLTASACILAGILVV | 402 |
| KCNS3 | KDD---------HTSSLTSIPICWWWATIS>M<TTVGYGDTHPVTLAGKLIASTCIICGILVV | 398 |
| KCNV1 | QSI---------PDTTFTSVPCAWWWATTS>M<TTVGYGDIRPDTTTGKIVAFMCILSGILVL | 420 |
| KCNV2 | HDV---------PSTNFTTIPHSWWWAAVS>I<STVGYGDMYPETHLGRFFAFLCIAFGIILN | 485 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.V310D | c.929T>A | Inherited Arrhythmia | LQTS | rs199472744 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Hum Mutat. 2001 18(5):451-7. 11668638 | ||
| p.V310I | c.928G>A | Inherited Arrhythmia | LQTS | rs199472745 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636 | |||
| 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 | Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels. J Physiol. 2005 563(Pt 2):359-68. 15649981 | |||
| Inherited Arrhythmia | LQTS | Cellular mechanisms underlying the increased disease severity seen for patients with long QT syndrome caused by compound mutations in KCNQ1. Biochem J. 2014 462(1):133-42. doi: 10.1042/BJ20140425. 24912595 | |||