| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN9A | N395K | Erythermalgia, primary | High | 9 | 15955112, 17430993 |
| SCN9A | N395K | Erythermalgia, primary | High | 9 | 17263810 |
| SCN4A | N440K | Myotonia | High | 9 | 22106717, 22914841 |
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 | LYQQTLRSAGKIY-MIFFMLVIFLGSFYLV>N<LILAVVAMAYEEQNQATIAETEEK-EKRFQ | 435 |
| SCN1A | LYQLTLRAAGKTY-MIFFVLVIFLGSFYLI>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ | 445 |
| SCN2A | LYQLTLRAAGKTY-MIFFVLVIFLGSFYLI>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ | 447 |
| SCN3A | LYQLTLRAAGKTY-MIFFVLVIFLGSFYLV>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ | 446 |
| SCN4A | LFQLTLRAAGKTY-MIFFVVIIFLGSFYLI>N<LILAVVAMAYAEQNEATLAEDKEK-EEEFQ | 469 |
| SCN7A | LYHQILYASGKVY-MIFFVVVSFLFSFYMA>S<LFLGILAMAYEEEKQRVGEISKKI-EPKFQ | 416 |
| SCN8A | LYQLTLRAAGKTY-MIFFVLVIFVGSFYLV>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFK | 433 |
| SCN9A | LYQQTLRAAGKTY-MIFFVVVIFLGSFYLI>N<LILAVVAMAYEEQNQANIEEAKQK-ELEFQ | 424 |
| SCN10A | LYQQTLRTSGKIY-MIFFVLVIFLGSFYLV>N<LILAVVTMAYEEQNQATTDEIEAK-EKKFQ | 419 |
| SCN11A | LYQQTLRTTGLYS-VFFFIVVIFLGSFYLI>N<LTLAVVTMAYEEQNKNVAAEIEAK-EKMFQ | 422 |
| CACNA1A | LLYNSNDASGNTWNWLYFIPLIIIGSFFML>N<LVLGVLSGEFAKERERVENRRAFLKLRRQQ | 383 |
| CACNA1B | ILYNTNDAAGNTWNWLYFIPLIIIGSFFML>N<LVLGVLSGEFAKERERVENRRAFLKLRRQQ | 379 |
| CACNA1C | VLYWVNDAVGRDWPWIYFVTLIIIGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKLREKQ | 428 |
| CACNA1D | VLYWVNDAIGWEWPWVYFVSLIILGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKLREKQ | 429 |
| CACNA1E | VLYNTNDALGATWNWLYFIPLIIIGSFFVL>N<LVLGVLSGEFAKERERVENRRAFMKLRRQQ | 374 |
| CACNA1F | VLYWMQDAMGYELPWVYFVSLVIFGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKQREKQ | 395 |
| CACNA1G | IMYFVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQRESQLMREQRVRFLS | 418 |
| CACNA1H | IMYYVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQRESQLMREQRARHLS | 442 |
| CACNA1I | IMYYVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQREHRLMLEQRQRYLS | 421 |
| CACNA1S | VLYWVNDAIGNEWPWIYFVTLILLGSFFIL>N<LVLGVLSGEFTKEREKAKSRGTFQKLREKQ | 357 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.N406K | c.1218C>G | Inherited Arrhythmia | LQTS | rs199473108 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | ||
| p.N406S | c.1217A>G | Inherited Arrhythmia | BrS | rs199473568 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2005 16(5):486-93. 15877619 | ||
| Inherited Arrhythmia | BrS | A paradoxical effect of lidocaine for the N406S mutation of SCN5A associated with Brugada syndrome. Int J Cardiol. 2007 121(3):239-48. 17445919 | |||
| Inherited Arrhythmia | BrS | Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A. J Cardiovasc Electrophysiol. 2005 16(4):378-83. 15828879 | |||
| p.N406K | c.1218C>A | Inherited Arrhythmia | LQTS | rs199473108 | SIFT: deleterious Polyphen: possibly damaging |
| Reports | 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 | Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench. J Cardiovasc Electrophysiol. 2014 25(1):66-73. doi: 10.1111/jce.12270. 24112685 | |||