| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CACNA1S | V876E | Hypokalaemic periodic paralysis | High | 9 | 19779499 |
| SCN2A | V1282F | Schizophrenia | High | 9 | 26555645 |
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 | EMLLKWVAYGF----KKYFTNAWCWLDFLI>V<DVSLVSLVAN-T----LGFAEMGPIKSLRT | 1304 |
| SCN1A | EMLLKWVAYGY----QTYFTNAWCWLDFLI>V<DVSLVSLTAN-A----LGYSELGAIKSLRT | 1317 |
| SCN2A | EMLLKWVAYGF----QVYFTNAWCWLDFLI>V<DVSLVSLTAN-A----LGYSELGAIKSLRT | 1307 |
| SCN3A | EMLLKWVAYGF----QTYFTNAWCWLDFLI>V<DVSLVSLVAN-A----LGYSELGAIKSLRT | 1305 |
| SCN4A | EMLLKWVAYGF----KVYFTNAWCWLDFLI>V<DVSIISLVAN-W----LGYSELGPIKSLRT | 1130 |
| SCN7A | EMLLKWMAYGF----KAYFSNGWYRLDFVV>V<IVFCLSLIGK-T----RE--E---LKPLIS | 1028 |
| SCN8A | EMLLKWTAYGF----VKFFTNAWCWLDFLI>V<AVSLVSLIAN-A----LGYSELGAIKSLRT | 1297 |
| SCN9A | EMLLKWIAYGY----KTYFTNAWCWLDFLI>V<DVSLVTLVAN-T----LGYSDLGPIKSLRT | 1280 |
| SCN10A | EMLLKWVAYGF----KKYFTNAWCWLDFLI>V<NISLISLTAK-I----LEYSEVAPIKALRT | 1251 |
| SCN11A | EMVLKWVAFGF----GKYFTSAWCCLDFII>V<IVSVTTLI---------N---LMELKSFRT | 1148 |
| CACNA1A | EMVIKMIDLGLVLHQGAYFRDLWNILDFIV>V<SGALVAFAFTGN----SKGKDINTIKSLRV | 1347 |
| CACNA1B | EMVIKMIDLGLLLHPGAYFRDLWNILDFIV>V<SGALVAFAFS-G----SKGKDINTIKSLRV | 1253 |
| CACNA1C | EIALKMTAYGAFLHKGSFCRNYFNILDLLV>V<SVSLISF----G----IQSSAINVVKILRV | 999 |
| CACNA1D | EILLKMTTFGAFLHKGAFCRNYFNLLDMLV>V<GVSLVSF----G----IQSSAISVVKILRV | 1005 |
| CACNA1E | EMVIKMIDQGLILQDGSYFRDLWNILDFVV>V<VGALVAFALANA-LGTNKGRDIKTIKSLRV | 1259 |
| CACNA1F | EILLKMTVFGAFLHRGSFCRSWFNMLDLLV>V<SVSLISF----G----IHSSAISVVKILRV | 970 |
| CACNA1G | EMTVKVVALGWCFGEQAYLRSSWNVLDGLL>V<LISVIDILVS-MVSD-SGTKILGMLRVLRL | 1382 |
| CACNA1H | EMMVKVVALGLLSGEHAYLQSSWNLLDGLL>V<LVSLVDIVVA-MASA-GGAKILGVLRVLRL | 1400 |
| CACNA1I | EMTLKVVSLGLYFGEQAYLRSSWNVLDGFL>V<FVSIIDIVVS-LASA-GGAKILGVLRVLRL | 1276 |
| CACNA1S | EIVLKMTTYGAFLHKGSFCRNYFNMLDLLV>V<AVSLISM----G----LESSAISVVKILRV | 898 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.V1279I | c.3835G>A | Cardiomyopathy | DCM | rs199473341 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Cardiomyopathy | DCM | SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism. J Am Coll Cardiol. 2011 57(21):2160-8. 21596231 | ||
| Unknown | New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. 2013 23299917 | ||||
| Unknown | Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381 | ||||
| Unknown | Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510 | ||||