| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | M1780T | Myoclonic epilepsy of infancy | High | 9 | 12821740 |
| SCN4A | M1592V | Hyperkalaemic periodic paralysis | High | 9 | 1659668, 19290024, 21404612, 21665479, 23801527, 18046642, 24943082, 24714718 |
| SCN2A | M1770L | Epileptic encephalopathy, neonatal | High | 9 | 26795593 |
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 SCN5A.
| SCN5A | RGD---CGSPAVGILFFTTYIIISFLIVVN>M<YIAIILENFSVATEESTEPLSEDDFDMFYE | 1796 |
| SCN1A | KGD---CGNPSVGIFFFVSYIIISFLVVVN>M<YIAVILENFSVATEESAEPLSEDDFEMFYE | 1810 |
| SCN2A | KGD---CGNPSVGIFFFVSYIIISFLVVVN>M<YIAVILENFSVATEESAEPLSEDDFEMFYE | 1800 |
| SCN3A | KGD---CGNPSVGIFFFVSYIIISFLVVVN>M<YIAVILENFSVATEESAEPLSEDDFEMFYE | 1795 |
| SCN4A | KGD---CGNPSIGICFFCSYIIISFLIVVN>M<YIAIILENFNVATEESSEPLGEDDFEMFYE | 1622 |
| SCN7A | RGD---CGNPSVGIFYFVSYILISWLIIVN>M<YIVVVMEFLNIASKKKNKTLSEDDFRKFFQ | 1520 |
| SCN8A | KGD---CGNPSVGIFFFVSYIIISFLIVVN>M<YIAIILENFSVATEESADPLSEDDFETFYE | 1790 |
| SCN9A | EGD---CGNPSVGIFYFVSYIIISFLVVVN>M<YIAVILENFSVATEESTEPLSEDDFEMFYE | 1773 |
| SCN10A | RGD---CGSPAVGIIFFTTYIIISFLIMVN>M<YIAVILENFNVATEESTEPLSEDDFDMFYE | 1746 |
| SCN11A | SEN---CHLPGIATSYFVSYIIISFLIVVN>M<YIAVILENFNTATEESEDPLGEDDFDIFYE | 1628 |
| CACNA1A | T-R--ECGN-EFAYFYFVSFIFLCSFLMLN>L<FVAVIMDNFEYLTRDSSI-LGPHHLDEYVR | 1834 |
| CACNA1B | A-NATECGS-DFAYFYFVSFIFLCSFLMLN>L<FVAVIMDNFEYLTRDSSI-LGPHHLDEFIR | 1732 |
| CACNA1C | GETP--CGS-SFAVFYFISFYMLCAFLIIN>L<FVAVIMDNFDYLTRDWSI-LGPHHLDEFKR | 1499 |
| CACNA1D | -EYT--CGS-NFAIVYFISFYMLCAFLIIN>L<FVAVIMDNFDYLTRDWSI-LGPHHLDEFKR | 1507 |
| CACNA1E | N-E--RCGT-DLAYVYFVSFIFFCSFLMLN>L<FVAVIMDNFEYLTRDSSI-LGPHHLDEFVR | 1746 |
| CACNA1F | -EFT--CGS-NFAIAYFISFFMLCAFLIIN>L<FVAVIMDNFDYLTRDWSI-LGPHHLDEFKR | 1464 |
| CACNA1G | ------YNT-VISPIYFVSFVLTAQFVLVN>V<VIAVLMKHLEESNKEAKE---EAELEAELE | 1872 |
| CACNA1H | --LS--YLP-ALSPVYFVTFVLVAQFVLVN>V<VVAVLMKHLEESNKEARE---DAELDAEIE | 1881 |
| CACNA1I | --LS--SLQ-FVSPLYFVSFVLTAQFVLIN>V<VVAVLMKHLDDSNKEAQE---DAEMDAELE | 1751 |
| CACNA1S | -EYT--CGT-NFAYYYFISFYMLCAFLVIN>L<FVAVIMDNFDYLTRDWSI-LGPHHLDEFKA | 1404 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.M1766L | c.5296A>C | Inherited Arrhythmia | LQTS | rs199473310 | SIFT: deleterious Polyphen: possibly damaging |
| Reports | Inherited Arrhythmia | LQTS | A novel SCN5A arrhythmia mutation, M1766L, with expression defect rescued by mexiletine. Cardiovasc Res. 2002 55(2):279-89. 12123767 | ||
| 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 | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| p.M1766V | c.5296A>G | Inherited Arrhythmia | LQTS | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | LQTS | Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm. 2013 10(3):378-82. doi: 10.1016/j.hrthm.2012.11.006. 23174487 | ||
| p.M1766T | c.5297T>C | Inherited Arrhythmia | BrS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | BrS | A comprehensive electrocardiographic, molecular, and echocardiographic study of Brugada syndrome: validation of the 2013 diagnostic criteria. Heart Rhythm. 2014 11(7):1176-83. doi: 10.1016/j.hrthm.2014.04.010. 24721456 | ||
| p.Met1766Lys | c.5297T>A | Unknown | SIFT: Polyphen: | ||