| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R859C | Generalized epilepsy with febrile seizures plus | High | 9 | 16525050, 25576396 |
| SCN4A | R669H | Hypokalaemic periodic paralysis | High | 9 | 10599760, 18162704, 21881211, 25024265 |
| CACNA1S | R528G | Hypokalaemic periodic paralysis | High | 9 | 15726306, 19822448 |
| CACNA1S | R528H | Hypokalaemic periodic paralysis | High | 9 | 7987325, 8605978, 9512357, 23187123, 19225109, 11034874, 7847370, 11808349 |
| CACNA1A | R583Q | Hemiplegic migraine and ataxia | High | 9 | 10408534, 19624685, 23407676, 12707077, 12707077, 22527033, 25969684, 24498617, 10734061, 26814174 |
| SCN1A | R859H | Generalized epilepsy with febrile seizures plus | High | 9 | 21864321, 24277604 |
| CACNA1S | R528C | Hypokalaemic periodic paralysis | High | 9 | 25430699 |
| SCN2A | R850P | Schizophrenia | High | 9 | 26555645 |
| SCN2A | R850X | Intellectual disability | High | 9 | 26350204 |
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 | IFDSIIVILSLMELGLSRMS-----NLSVL>R<SFRLLRVFKLAKSWPTLNTLIKIIGNSVGA | 838 |
| SCN1A | IFDGFIVTLSLVELGLANVE-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 889 |
| SCN2A | IFDGFIVSLSLMELGLANVE-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 880 |
| SCN3A | IFDGIIVSLSLMELGLSNVE-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 881 |
| SCN4A | IFDSIIVTLSLVELGLANVQ-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 699 |
| SCN7A | IFDSMIVFHGLIELCLANVA-----GMALL>R<LFRMLRIFKLGKYWPTFQILMWSLSNSWVA | 626 |
| SCN8A | IFDGFIVSLSLMELSLADVE-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 874 |
| SCN9A | IFDSLIVTLSLVELFLADVE-----GLSVL>R<SFRLLRVFKLAKSWPTLNMLIKIIGNSVGA | 854 |
| SCN10A | IFDCIIVTVSLLELGVAKKG-----SLSVL>R<SFRLLRVFKLAKSWPTLNTLIKIIGNSVGA | 786 |
| SCN11A | IFDSIVALLSFADVMNCVLQKR---SWPFL>R<SFRVLRVFKLAKSWPTLNTLIKIIGNSVGA | 700 |
| CACNA1A | CFDCGVIIGSIFEVIWAVIKPGTSFGISVL>R<ALRLLRIFKVTKYWASLRNLVVSLLNSMKS | 613 |
| CACNA1B | CFDFGVIVGSVFEVVWAAIKPGSSFGISVL>R<ALRLLRIFKVTKYWSSLRNLVVSLLNSMKS | 609 |
| CACNA1C | RFDCFVVCGGILETILVETKIMSPLGISVL>R<CVRLLRIFKITRYWNSLSNLVASLLNSVRS | 650 |
| CACNA1D | RFDCFVVCGGITETILVELEIMSPLGISVF>R<CVRLLRIFKVTRHWTSLSNLVASLLNSMKS | 669 |
| CACNA1E | CFDFGVTVGSIFEVVWAIFRPGTSFGISVL>R<ALRLLRIFKITKYWASLRNLVVSLMSSMKS | 602 |
| CACNA1F | RFDCFVVCGGILETTLVEVGAMQPLGISVL>R<CVRLLRIFKVTRHWASLSNLVASLLNSMKS | 655 |
| CACNA1G | IFDGVIVVISVWEIVGQQGG-----GLSVL>R<TFRLMRVLKLVRFLPALQRQLVVLMKTMDN | 864 |
| CACNA1H | IFDGIIVVISVWEIVGQADG-----GLSVL>R<TFRLLRVLKLVRFLPALRRQLVVLVKTMDN | 914 |
| CACNA1I | IFDSIIVIISIWEIVGQADG-----GLSVL>R<TFRLLRVLKLVRFMPALRRQLVVLMKTMDN | 761 |
| CACNA1S | RFDCFVVCSGILEILLVESGAMTPLGISVL>R<CIRLLRIFKITKYWTSLSNLVASLLNSIRS | 558 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R808P | c.2423G>C | Inherited Arrhythmia | LQTS,BrS | rs199473160 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat. 2009 30(11):1486-511. 19862833 | ||
| 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.R808C | c.2422C>T | Inherited Arrhythmia | BrS | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | BrS | Novel sodium channel SCN5A mutations in Brugada syndrome patients from Greece. Int J Cardiol. 2010 145(1):45-8. 19406494 | ||
| p.R808H | c.2423G>A | Putative Benign | SIFT: Polyphen: | ||