| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R1639G | Dravet syndrome | High | 6 | 18930999 |
| SCN4A | R1451C | Periodic paralysis | High | 6 | 19201608 |
| CACNA1S | R1239G | Hypokalaemic periodic paralysis | High | 6 | 8004673, 21891927 |
| CACNA1S | R1239H | Hypokalaemic periodic paralysis | High | 6 | 7847370, 19225109, 10639629, 11555352 |
| CACNA1A | R1665Q | Spinocerebellar ataxia 6 | High | 6 | 16325861 |
| SCN2A | R1629L | Epileptic encephalopathy, early onset | High | 6 | 23935176 |
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 | ------------------KYFFSPTLFRVI>R<LARIGRILRLIRGAKGIRTLLFALMMSLPA | 1656 |
| SCN1A | ------------------KYFVSPTLFRVI>R<LARIGRILRLIKGAKGIRTLLFALMMSLPA | 1669 |
| SCN2A | ------------------KYFVSPTLFRVI>R<LARIGRILRLIKGAKGIRTLLFALMMSLPA | 1659 |
| SCN3A | ------------------KYFVSPTLFRVI>R<LARIGRILRLIKGAKGIRTLLFALMMSLPA | 1654 |
| SCN4A | ------------------KYFVSPTLFRVI>R<LARIGRVLRLIRGAKGIRTLLFALMMSLPA | 1481 |
| SCN7A | ------------------SYLVPPSLVQLI>L<LSRIIHMLRLGKGPKVFHNLMLPLMLSLPA | 1379 |
| SCN8A | ------------------KYFVSPTLFRVI>R<LARIGRILRLIKGAKGIRTLLFALMMSLPA | 1650 |
| SCN9A | ------------------TYFVSPTLFRVI>R<LARIGRILRLVKGAKGIRTLLFALMMSLPA | 1632 |
| SCN10A | -----------------LQSYFSPTLFRVI>R<LARIGRILRLIRAAKGIRTLLFALMMSLPA | 1606 |
| SCN11A | -----------------EHIPFPPTLFRIV>R<LARIGRILRLVRAARGIRTLLFALMMSLPS | 1496 |
| CACNA1A | --------------------FINLSFLRLF>R<A---ARLIKLLRQGYTIRILLWTFVQSFKA | 1691 |
| CACNA1B | ------------------NNFINLSFLRLF>R<A---ARLIKLLRQGYTIRILLWTFVQSFKA | 1599 |
| CACNA1C | --HTQ----CSPSMNAEENSRISITFFRLF>R<V---MRLVKLLSRGEGIRTLLWTFIKSFQA | 1359 |
| CACNA1D | --SENVPVPTATPGNSEESNRISITFFRLF>R<V---MRLVKLLSRGEGIRTLLWTFIKSFQA | 1369 |
| CACNA1E | -----------------NTSGFNMSFLKLF>R<A---ARLIKLLRQGYTIRILLWTFVQSFKA | 1606 |
| CACNA1F | --HLG----E----SSEDSSRISITFFRLF>R<V---MRLVKLLSKGEGIRTLLWTFIKSFQA | 1326 |
| CACNA1G | -----------------ASLPINPTIIRIM>R<VLRIARVLKLLKMAVGMRALLDTVMQALPQ | 1742 |
| CACNA1H | -----------------AALPINPTIIRIM>R<VLRIARVLKLLKMATGMRALLDTVVQALPQ | 1748 |
| CACNA1I | -----------------AALPINPTIIRIM>R<VLRIARVLKLLKMATGMRALLDTVVQALPQ | 1618 |
| CACNA1S | SGGLYCLGGGCGNVDPDESARISSAFFRLF>R<V---MRLIKLLSRAEGVRTLLWTFIKSFQA | 1266 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R1626H | c.4877G>A | Inherited Arrhythmia | LQTS,AF | rs199473283 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. Scand J Clin Lab Invest. 2008 68(5):362-8. 18752142 | ||
| 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 | High prevalence of long QT syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation. Circ Cardiovasc Genet. 2012 5(4):450-9. doi: 10.1161/CIRCGENETICS.111.962597. 22685113 | |||
| Inherited Arrhythmia | LQTS | Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. Eur Heart J. 2015 36(37):2523-9. doi: 10.1093/eurheartj/ehv297. 26159999 | |||
| p.R1626P | c.4877G>C | Inherited Arrhythmia | LQTS | rs199473283 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation. 2000 102(9):945-7. 10961955 | ||
| 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 | Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation. 2007 116(10):1137-44. 17698727 | |||
| Inherited Arrhythmia | LQTS | Impaired stretch modulation in potentially lethal cardiac sodium channel mutants. Channels (Austin). 2010 4(1):12-21. 20090423 | |||