| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNA1 | F184C | Episodic ataxia / myokymia | Medium | 9 | 8541859, 10383630, 8845167, 9526001, 26338330 |
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 | YNFLERPT-GWKCFVYHFAVFLIVLVCLIF>S<VLSTIEQYA--------------------- | 149 |
| KCNQ2 | YNVLERPR-G-WAFIYHAYVFLLVFSCLVL>S<VFSTIKEYE--------------------- | 119 |
| KCNQ3 | YDALERPR-G-WALLYHALVFLIVLGCLIL>A<VLTTFKEYE--------------------- | 149 |
| KCNQ4 | YNVLERPR-G-WAFVYHVFIFLLVFSCLVL>S<VLSTIQEHQ--------------------- | 125 |
| KCNQ5 | YNVLERPR-G-WAFIYHAFVFLLVFGCLIL>S<VFSTIPEHT--------------------- | 153 |
| KCNA1 | WLLFEYPESSGPARVIAIVSVMVILISIVI>F<CLETLPELKDDK-DF--------TG----- | 200 |
| KCNA10 | WLLFEYPESSSAARAVAVVSVLVVVISITI>F<CLETLPEFREDR-EL--------KV----- | 249 |
| KCNA2 | WLLFEYPESSGPARIIAIVSVMVILISIVS>F<CLETLPIFRDEN-ED--------MHGSG-- | 199 |
| KCNA3 | WLLFEYPESSGPARGIAIVSVLVILISIVI>F<CLETLPEFRDEK-DY--------PA-ST-- | 269 |
| KCNA4 | WLLFEYPESSSPARGIAIVSVLVILISIVI>F<CLETLPEFRDDR-DL--------VM-AL-- | 342 |
| KCNA5 | WLIFEYPESSGSARAIAIVSVLVILISIIT>F<CLETLPEFRDER-ELLRHPPAP-------- | 288 |
| KCNA6 | WLLFEYPESSGPARGIAIVSVLVILISIVI>F<CLETLPQFRVDG-RGGNNGGVSRVS-PVSR | 219 |
| KCNA7 | WLLFEFPESSQAARVLAVVSVLVILVSIVV>F<CLETLPDFRDDR-DGTGL-----AA-AA-- | 181 |
| KCNB1 | WDLLEKPNSSVAAKILAIISIMFIVLSTIA>L<SLNTLPELQSLD-EF--------GQ----- | 222 |
| KCNB2 | WDLLEKPNSSVAAKILAIVSILFIVLSTIA>L<SLNTLPELQETD-EF--------GQ----- | 226 |
| KCNC1 | WALFEDPYSSRYARYVAFASLFFILVSITT>F<CLETHERFNPIV-NK--------TE-I--- | 224 |
| KCNC2 | WALFEDPYSSRAARFIAFASLFFILVSITT>F<CLETHEAFNI---VK--------NK-T--- | 261 |
| KCNC3 | WALFEDPYSSRAARYVAFASLFFILISITT>F<CLETHEGFIHIS-NK--------TV-T--- | 324 |
| KCNC4 | WALFEDPYSSRAARVVAFASLFFILVSITT>F<CLETHEAFNI---DR-NV-----TE-I--- | 260 |
| KCND1 | WRAFENPHTSTAALVFYYVTGFFIAVSVIA>N<VVETIPCRGSAR-RS--------SR----- | 219 |
| KCND2 | WRAFENPHTSTMALVFYYVTGFFIAVSVIA>N<VVETVPCGS-SP-GH--------IK----- | 217 |
| KCND3 | WRAFENPHTSTLALVFYYVTGFFIAVSVIT>N<VVETVPCGT-VP-G---------SK----- | 214 |
| KCNF1 | WKFLEKPESSCPARVVAVLSFLLILVSSVV>M<CMGTIPELQVLD-AE--------GN----- | 215 |
| KCNG1 | RDMVERPHSGLPGKVFACLSVLFVTVTAVN>L<SVSTLPSLREEEE-Q--------GH----- | 260 |
| KCNG2 | RDVVDNPHSGLAGKLFACVSVSFVAVTAVG>L<CLSTMPDIRAEEE-R--------GE----- | 210 |
| KCNG3 | RRTFEEPTSSLAAQILASVSVVFVIVSMVV>L<CASTLPDWRN-AAAD--------NR----- | 204 |
| KCNG4 | REMVENPQSGLPGKVFACLSILFVATTAVS>L<CVSTMPDLRAEED-Q--------GE----- | 254 |
| KCNS1 | WLTMENPGYSLPSKLFSCVSISVVLASIAA>M<CIHSLPEYQARE-AA--------AA----- | 253 |
| KCNS2 | WLALDNPGYSVLSRVFSILSILVVMGSIIT>M<CLNSLPDFQIPD-SQ--------GN----- | 220 |
| KCNS3 | WIRMENPAYCLSAKLIAISSLSVVLASIVA>M<CVHSMSEFQNED-GE--------------- | 216 |
| KCNV1 | WNILEKPGSSTAARIFGVISIIFVVVSIIN>M<ALMSAEL-----------------S----- | 235 |
| KCNV2 | WNLMEKPFSSVAAKAIGVASSTFVLVSVVA>L<ALNTVEEMQQHS-GQ--------GE----- | 293 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.S140G | c.418A>G | Inherited Arrhythmia | LQTS,AF | rs120074192 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | AF | KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science. 2003 299(5604):251-4. 12522251 | ||
| Inherited Arrhythmia | AF | Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet. 2004 75(5):899-905. 15368194 | |||
| Inherited Arrhythmia | AF | Human KCNQ1 S140G mutation is associated with atrioventricular blocks. Heart Rhythm. 2007 4(5):611-8. 17467630 | |||
| Inherited Arrhythmia | AF | Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels. J Physiol. 2008 586(Pt 17):4179-91. 18599533 | |||
| Inherited Arrhythmia | AF | The S140G KCNQ1 atrial fibrillation mutation affects 'I(KS)' profile during both atrial and ventricular action potentials. J Physiol Pharmacol. 2010 61(6):759-64. 21224508 | |||
| Inherited Arrhythmia | AF | Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. J Gen Physiol. 2012 139(2):135-44. doi: 10.1085/jgp.201110672. 22250012 | |||
| Inherited Arrhythmia | LQTS | Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538 | |||
| Inherited Arrhythmia | AF | Pro-arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation - insights from modelling. J Physiol. 2012 590(Pt 18):4501-14. doi: 10.1113/jphysiol.2012.229 22508963 | |||
| Inherited Arrhythmia | AF | Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Circ Arrhythm Electrophysiol. 2013 6(5):960-6. doi: 10.1161/CIRCEP.113.000439. 24006450 | |||
| Inherited Arrhythmia | AF | In silico investigation of a KCNQ1 mutation associated with familial atrial fibrillation. J Electrocardiol. 2014 47(2):158-65. doi: 10.1016/j.jelectrocard.2013.12. 24411289 | |||
| p.S140R | c.420C>A | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction. Cardiology. 2016 133(2):73-8. doi: 10.1159/000440608. 26496715 | ||