Paralogue Annotation for SCN5A residue 1275

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1275
Reference Amino Acid: D - Aspartate
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1275

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CACNA1FD944YNight blindness, congenital stationary, incompleteHigh9 19578023
SCN1AD1288NDravet syndrome C ?High9 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.

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See full Alignment of Paralogues

Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.D1275Nc.3823G>A Inherited ArrhythmiaBrS,DCMSIFT: deleterious
Polyphen: probably damaging
ReportsOther 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 ArrhythmiaBrS 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 ArrhythmiaBrS 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
CardiomyopathyDCM 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 ArrhythmiaBrS 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.Asp1275Tyrc.3823G>T UnknownSIFT: