| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R1245Q | Myoclonic epilepsy of infancy | High | 7 | 17054684, 21906962 |
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 | VEHSWFETFIIFMILLSSGALAFEDIYLEE>R<KTIKVLLEYADKMFTYVFVLEMLLKWVAYG | 1262 |
| SCN1A | VEHNWFETFIVFMILLSSGALAFEDIYIDQ>R<KTIKTMLEYADKVFTYIFILEMLLKWVAYG | 1275 |
| SCN2A | VEHNWFETFIVFMILLSSGALAFEDIYIEQ>R<KTIKTMLEYADKVFTYIFILEMLLKWVAYG | 1265 |
| SCN3A | VEHNWFETFIVFMILLSSGALAFEDIYIEQ>R<KTIKTMLEYADKVFTYIFILEMLLKWVAYG | 1263 |
| SCN4A | VEHNWFETFIVFMILLSSGALAFEDIYIEQ>R<RVIRTILEYADKVFTYIFIMEMLLKWVAYG | 1088 |
| SCN7A | VENNWFKCFIGLVTLLSTGTLAFEDIYMDQ>R<KTIKILLEYADMIFTYIFILEMLLKWMAYG | 991 |
| SCN8A | VEHNWFETFIIFMILLSSGALAFEDIYIEQ>R<KTIRTILEYADKVFTYIFILEMLLKWTAYG | 1255 |
| SCN9A | VEHSWFESFIVLMILLSSGALAFEDIYIER>K<KTIKIILEYADKIFTYIFILEMLLKWIAYG | 1238 |
| SCN10A | VEHSWFESFIIFMILLSSGSLAFEDYYLDQ>K<PTVKALLEYTDRVFTFIFVFEMLLKWVAYG | 1209 |
| SCN11A | VKHSWFESFIIFVILLSSGALIFEDVHLEN>Q<PKIQELLNCTDIIFTHIFILEMVLKWVAFG | 1113 |
| CACNA1A | LNLRYFEMCILMVIAMSSIALAAEDPV-QP>N<APRNNVLRYFDYVFTGVFTFEMVIKMIDLG | 1300 |
| CACNA1B | VTMRYFEVVILVVIALSSIALAAEDPV-RT>D<SPRNNALKYLDYIFTGVFTFEMVIKMIDLG | 1207 |
| CACNA1C | VNDTIFTNLILFFILLSSISLAAEDPV-QH>T<SFRNHILFYFDIVFTTIFTIEIALKMTAYG | 956 |
| CACNA1D | INHHIFTNLILVFIMLSSAALAAEDPI-RS>H<SFRNTILGYFDYAFTAIFTVEILLKMTTFG | 962 |
| CACNA1E | VNLRYFEMCILLVIAASSIALAAEDPV-LT>N<SERNKVLRYFDYVFTGVFTFEMVIKMIDQG | 1209 |
| CACNA1F | IHHHVFTNLILVFIILSSVSLAAEDPI-RA>H<SFRNHILGYFDYAFTSIFTVEILLKMTVFG | 927 |
| CACNA1G | ITHKMFDHVVLVIIFLNCITIAMERPKIDP>H<SAERIFLTLSNYIFTAVFLAEMTVKVVALG | 1333 |
| CACNA1H | ITHKMFDHVVLVFIFLNCVTIALERPDIDP>G<STERVFLSVSNYIFTAIFVAEMMVKVVALG | 1351 |
| CACNA1I | IAHKLFDYVVLAFIFLNCITIALERPQIEA>G<STERIFLTVSNYIFTAIFVGEMTLKVVSLG | 1227 |
| CACNA1S | VNATWFTNFILLFILLSSAALAAEDPI-RA>D<SMRNQILKHFDIGFTSVFTVEIVLKMTTYG | 855 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R1232Q | c.3695G>A | Inherited Arrhythmia | BrS | rs199473206 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283 | ||
| Inherited Arrhythmia | BrS | Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861 | |||
| p.R1232W | c.3694C>T | Inherited Arrhythmia | BrS | rs199473207 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Other Cardiac Phenotype | Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998 392(6673):293-6. 9521325 | |||
| Inherited Arrhythmia | BrS | Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009 6(3):341-8. 19251209 | |||
| Inherited Arrhythmia | BrS | An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283 | |||
| Inherited Arrhythmia | BrS | Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome. Int Heart J. 2011 52(1):27-31. 21321465 | |||
| Other Cardiac Phenotype | Functional suppression of sodium channels by beta(1)-subunits as a molecular mechanism of idiopathic ventricular fibrillation. J Mol Cell Cardiol. 2000 32(10):1873-84. 11013131 | ||||
| Other Cardiac Phenotype | Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circ Res. 2002 90(1):E11-6. 11786529 | ||||
| Inherited Arrhythmia | BrS | Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861 | |||