| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R1657C | Generalized epilepsy with febrile seizures plus | High | 9 | 14672992 |
| SCN1A | R1657H | Cryptogenic focal epilepsy | High | 9 | 17347258, 21719429 |
| CACNA1A | R1680C | Episodic ataxia 2 | High | 9 | 20129625 |
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 | KYFFSPTLFRVIRLARIGRILRLIRGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYSIF | 1674 |
| SCN1A | KYFVSPTLFRVIRLARIGRILRLIKGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYAIF | 1687 |
| SCN2A | KYFVSPTLFRVIRLARIGRILRLIKGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYAIF | 1677 |
| SCN3A | KYFVSPTLFRVIRLARIGRILRLIKGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYAIF | 1672 |
| SCN4A | KYFVSPTLFRVIRLARIGRVLRLIRGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYSIF | 1499 |
| SCN7A | SYLVPPSLVQLILLSRIIHMLRLGKGPKVF>H<NLMLPLMLSLPALLNIILLIFLVMFIYAVF | 1397 |
| SCN8A | KYFVSPTLFRVIRLARIGRILRLIKGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIFSIF | 1668 |
| SCN9A | TYFVSPTLFRVIRLARIGRILRLVKGAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYAIF | 1650 |
| SCN10A | QSYFSPTLFRVIRLARIGRILRLIRAAKGI>R<TLLFALMMSLPALFNIGLLLFLVMFIYSIF | 1624 |
| SCN11A | HIPFPPTLFRIVRLARIGRILRLVRAARGI>R<TLLFALMMSLPSLFNIGLLLFLIMFIYAIL | 1514 |
| CACNA1A | --FINLSFLRLFRA---ARLIKLLRQGYTI>R<ILLWTFVQSFKALPYVCLLIAMLFFIYAII | 1709 |
| CACNA1B | NNFINLSFLRLFRA---ARLIKLLRQGYTI>R<ILLWTFVQSFKALPYVCLLIAMLFFIYAII | 1617 |
| CACNA1C | NSRISITFFRLFRV---MRLVKLLSRGEGI>R<TLLWTFIKSFQALPYVALLIVMLFFIYAVI | 1377 |
| CACNA1D | SNRISITFFRLFRV---MRLVKLLSRGEGI>R<TLLWTFIKSFQALPYVALLIAMLFFIYAVI | 1387 |
| CACNA1E | TSGFNMSFLKLFRA---ARLIKLLRQGYTI>R<ILLWTFVQSFKALPYVCLLIAMLFFIYAII | 1624 |
| CACNA1F | SSRISITFFRLFRV---MRLVKLLSKGEGI>R<TLLWTFIKSFQALPYVALLIAMIFFIYAVI | 1344 |
| CACNA1G | SLPINPTIIRIMRVLRIARVLKLLKMAVGM>R<ALLDTVMQALPQVGNLGLLFMLLFFIFAAL | 1760 |
| CACNA1H | ALPINPTIIRIMRVLRIARVLKLLKMATGM>R<ALLDTVVQALPQVGNLGLLFMLLFFIYAAL | 1766 |
| CACNA1I | ALPINPTIIRIMRVLRIARVLKLLKMATGM>R<ALLDTVVQALPQVGNLGLLFMLLFFIYAAL | 1636 |
| CACNA1S | SARISSAFFRLFRV---MRLIKLLSRAEGV>R<TLLWTFIKSFQALPYVALLIVMLFFIYAVI | 1284 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R1644C | c.4930C>T | Inherited Arrhythmia | LQTS,BrS | rs199473287 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation. 2005 112(24):3680-7. 16344400 | ||
| 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 | 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.R1644H | c.4931G>A | Inherited Arrhythmia | LQTS | rs28937316 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 4(9):1603-7. 8541846 | ||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636 | |||
| 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 | |||
| Inherited Arrhythmia | LQTS | Multiple mechanisms of Na+ channel--linked long-QT syndrome. Circ Res. 1996 78(5):916-24. 8620612 | |||
| Inherited Arrhythmia | LQTS | Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc Natl Acad Sci U S A. 1996 93(23):13200-5. 8917568 | |||
| p.R1644L | c.4931G>T | Putative Benign | SIFT: Polyphen: | ||