| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CACNA1F | D944Y | Night blindness, congenital stationary, incomplete | High | 9 | 19578023 |
| SCN1A | D1288N | Dravet syndrome C ? | High | 9 | 21248271 |
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 | VFVLEMLLKWVAYGF----KKYFTNAWCWL>D<FLIVDVSLVSLVAN-T----LGFAEMGPIK | 1300 |
| SCN1A | IFILEMLLKWVAYGY----QTYFTNAWCWL>D<FLIVDVSLVSLTAN-A----LGYSELGAIK | 1313 |
| SCN2A | IFILEMLLKWVAYGF----QVYFTNAWCWL>D<FLIVDVSLVSLTAN-A----LGYSELGAIK | 1303 |
| SCN3A | IFILEMLLKWVAYGF----QTYFTNAWCWL>D<FLIVDVSLVSLVAN-A----LGYSELGAIK | 1301 |
| SCN4A | IFIMEMLLKWVAYGF----KVYFTNAWCWL>D<FLIVDVSIISLVAN-W----LGYSELGPIK | 1126 |
| SCN7A | IFILEMLLKWMAYGF----KAYFSNGWYRL>D<FVVVIVFCLSLIGK-T----RE--E---LK | 1024 |
| SCN8A | IFILEMLLKWTAYGF----VKFFTNAWCWL>D<FLIVAVSLVSLIAN-A----LGYSELGAIK | 1293 |
| SCN9A | IFILEMLLKWIAYGY----KTYFTNAWCWL>D<FLIVDVSLVTLVAN-T----LGYSDLGPIK | 1276 |
| SCN10A | IFVFEMLLKWVAYGF----KKYFTNAWCWL>D<FLIVNISLISLTAK-I----LEYSEVAPIK | 1247 |
| SCN11A | IFILEMVLKWVAFGF----GKYFTSAWCCL>D<FIIVIVSVTTLI---------N---LMELK | 1144 |
| CACNA1A | VFTFEMVIKMIDLGLVLHQGAYFRDLWNIL>D<FIVVSGALVAFAFTGN----SKGKDINTIK | 1343 |
| CACNA1B | VFTFEMVIKMIDLGLLLHPGAYFRDLWNIL>D<FIVVSGALVAFAFS-G----SKGKDINTIK | 1249 |
| CACNA1C | IFTIEIALKMTAYGAFLHKGSFCRNYFNIL>D<LLVVSVSLISF----G----IQSSAINVVK | 995 |
| CACNA1D | IFTVEILLKMTTFGAFLHKGAFCRNYFNLL>D<MLVVGVSLVSF----G----IQSSAISVVK | 1001 |
| CACNA1E | VFTFEMVIKMIDQGLILQDGSYFRDLWNIL>D<FVVVVGALVAFALANA-LGTNKGRDIKTIK | 1255 |
| CACNA1F | IFTVEILLKMTVFGAFLHRGSFCRSWFNML>D<LLVVSVSLISF----G----IHSSAISVVK | 966 |
| CACNA1G | VFLAEMTVKVVALGWCFGEQAYLRSSWNVL>D<GLLVLISVIDILVS-MVSD-SGTKILGMLR | 1378 |
| CACNA1H | IFVAEMMVKVVALGLLSGEHAYLQSSWNLL>D<GLLVLVSLVDIVVA-MASA-GGAKILGVLR | 1396 |
| CACNA1I | IFVGEMTLKVVSLGLYFGEQAYLRSSWNVL>D<GFLVFVSIIDIVVS-LASA-GGAKILGVLR | 1272 |
| CACNA1S | VFTVEIVLKMTTYGAFLHKGSFCRNYFNML>D<LLVVAVSLISM----G----LESSAISVVK | 894 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.D1275N | c.3823G>A | Inherited Arrhythmia | BrS,DCM | rs137854618 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Other Cardiac Phenotype | A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill. Circ Res. 2003 92(1):14-22. 12522116 | |||
| Other Cardiac Phenotype | SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation. 2004 110(15):2163-7. 15466643 | ||||
| Other Cardiac Phenotype | SCN5A mutation associated with cardiac conduction defect and atrial arrhythmias. J Cardiovasc Electrophysiol. 2006 17(5):480-5. 16684018 | ||||
| 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 | |||
| Other Cardiac Phenotype | Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. J Cardiovasc Electrophysiol. 2010 21(5):564-73. 20384651 | ||||
| Other Cardiac Phenotype | Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010 5(6):e10985. 20539757 | ||||
| Other Cardiac Phenotype | Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro. Circulation. 2011 124(9):1001-11. 21824921 | ||||
| Other Cardiac Phenotype | A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. Circ Arrhythm Electrophysiol. 2012 5(1):163-72. 22247482 | ||||
| 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 | |||
| Other Cardiac Phenotype | A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death. J Mol Cell Cardiol. 2013 61:123-32. doi: 10.1016/j.yjmcc.2013.06.005. 23791817 | ||||
| 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 | |||
| Other Cardiac Phenotype | Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations. Circ Cardiovasc Genet. 2014 7(2):123-31. doi: 10.1161/CIRCGENETICS.113.000292. 24573164 | ||||
| Other Cardiac Phenotype | Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics. Circ Arrhythm Electrophysiol. 2014 7(3):511-7. doi: 10.1161/CIRCEP.113.001340. 24762805 | ||||
| Other Cardiac Phenotype | Loss-of-Function SCN5A Mutations Associated with Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture. Circ Arrhythm Electrophysiol. 2015 26111534 | ||||
| p.Asp1275Tyr | c.3823G>T | Unknown | SIFT: Polyphen: | ||