Paralogue Annotation for SCN5A residue 220

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 220
Reference Amino Acid: T - Threonine
Protein Domain: TM Domain 1

Paralogue Variants mapped to SCN5A residue 220

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AT217KMyoclonic epilepsy of infancyHigh9 17054684
SCN2AT218KEpilepsy of infancy with migrating focal seizuresHigh9 26291284

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.T220Ic.659C>T ConflictSIFT: deleterious
Polyphen: probably damaging
ReportsOther Cardiac Phenotype Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003 112(7):1019-28. 14523039
CardiomyopathyDCM Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005 293(4):447-54. 15671429
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 Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome. Circ Res. 2010 107(1):126-37. 20448214
Other Cardiac Phenotype Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010 5(6):e10985. 20539757
Inherited ArrhythmiaAF High prevalence of long QT syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation. Circ Cardiovasc Genet. 2012 5(4):450-9. doi: 10.1161/CIRCGENETICS.111.962597. 22685113
Other Cardiac Phenotype High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. Clin Genet. 2013 23414114
Other Cardiac Phenotype Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am J Hum Genet. 2013 93(4):631-40. doi: 10.1016/j.ajhg.2013.08.006. 24055113
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 Disease Phenotype Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome. Gastroenterology. 2014 146(7):1659-68. doi: 10.1053/j.gastro.2014.02.054. 24613995
Other Cardiac Phenotype The implications of familial incidental findings from exome sequencing: the NIH Undiagnosed Diseases Program experience. Genet Med. 2014 16(10):741-50. doi: 10.1038/gim.2014.29. 24784157
Other Cardiac Phenotype Compound heterozygous mutations in the SCN5A-encoded Nav1.5 cardiac sodium channel resulting in atrial standstill and His-Purkinje system disease. J Pediatr. 2014 165(5):1050-2. doi: 10.1016/j.jpeds.2014.07.036. 25171853
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
Other Cardiac Phenotype Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel. PLoS One. 2015 10(12):e0143588. doi: 10.1371/journal.pone.0143588 26636822