Paralogue Annotation for SCN5A residue 367

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 367
Reference Amino Acid: R - Arginine
Protein Domain: TM Domain 1


Paralogue Variants mapped to SCN5A residue 367

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AR377QGeneralized epilepsy with febrile seizures plusHigh9 18413471, 26096185
SCN1AR377LDravet syndromeHigh9 18076640

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.



SCN5AEGYRCLKAGENPDHGYTSFDSFAWAFLALF>R<LMTQDCWERLYQQTLRSAGKIY-MIFFMLV396
SCN1AEGYMCVKAGRNPNYGYTSFDTFSWAFLSLF>R<LMTQDFWENLYQLTLRAAGKTY-MIFFVLV406
SCN2AEGYICVKAGRNPNYGYTSFDTFSWAFLSLF>R<LMTQDFWENLYQLTLRAAGKTY-MIFFVLV408
SCN3AEGYICVKAGRNPNYGYTSFDTFSWAFLSLF>R<LMTQDYWENLYQLTLRAAGKTY-MIFFVLV407
SCN4AEGYECIKTGRNPNYGYTSYDTFSWAFLALF>R<LMTQDYWENLFQLTLRAAGKTY-MIFFVVI430
SCN7AEGYVCVKAGINPDQGFTNFDSFGWALFALF>R<LMAQDYPEVLYHQILYASGKVY-MIFFVVV377
SCN8AEGYQCMKAGRNPNYGYTSFDTFSWAFLALF>R<LMTQDYWENLYQLTLRAAGKTY-MIFFVLV394
SCN9AEGYTCVKIGRNPDYGYTSFDTFSWAFLALF>R<LMTQDYWENLYQQTLRAAGKTY-MIFFVVV385
SCN10ADGYICLKTSDNPDFNYTSFDSFAWAFLSLF>R<LMTQDSWERLYQQTLRTSGKIY-MIFFVLV380
SCN11AIQYECKHTKINPDYNYTNFDNFGWSFLAMF>R<LMTQDSWEKLYQQTLRTTGLYS-VFFFIVV383
CACNA1ANGTKCQPYWEGPNNGITQFDNILFAVLTVF>Q<CITMEGWTDLLYNSNDASGNTWNWLYFIPL343
CACNA1BGDTECREYWPGPNFGITNFDNILFAILTVF>Q<CITMEGWTDILYNTNDAAGNTWNWLYFIPL339
CACNA1C-GTVCKPGWDGPKHGITNFDNFAFAMLTVF>Q<CITMEGWTDVLYWVNDAVGRDWPWIYFVTL388
CACNA1DNGTECRSGWVGPNGGITNFDNFAFAMLTVF>Q<CITMEGWTDVLYWVNDAIGWEWPWVYFVSL389
CACNA1EAGYEC-KDWIGPNDGITQFDNILFAVLTVF>Q<CITMEGWTTVLYNTNDALGATWNWLYFIPL334
CACNA1FNQTECRGRWPGPNGGITNFDNFFFAMLTVF>Q<CVTMEGWTDVLYWMQDAMGYELPWVYFVSL355
CACNA1GYYTNCSAGEHNPFKGAINFDNIGYAWIAIF>Q<VITLEGWVDIMYFVMDAHSF-YNFIYFILL378
CACNA1HYYNVCRSGDSNPHNGAINFDNIGYAWIAIF>Q<VITLEGWVDIMYYVMDAHSF-YNFIYFILL402
CACNA1IYYNVCRTGSANPHKGAINFDNIGYAWIVIF>Q<VITLEGWVEIMYYVMDAHSF-YNFIYFILL381
CACNA1SNGSECRGGWPGPNHGITHFDNFGFSMLTVY>Q<CITMEGWTDVLYWVNDAIGNEWPWIYFVTL317
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R367Cc.1099C>T Inherited ArrhythmiaLQTS,BrSrs199473097SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol. 2002 40(2):350-6. 12106943
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 ArrhythmiaLQTS 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
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
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
p.R367Hc.1100G>A Inherited ArrhythmiaBrSrs28937318SIFT: deleterious
Polyphen: probably damaging
ReportsOther Cardiac Phenotype Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002 11(3):337-45. 11823453
Inherited ArrhythmiaBrS A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill. J Intern Med. 2004 255(1):137-42. 14687250
Inherited ArrhythmiaBrS Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A:. J Cardiovasc Electrophysiol. 2004 15(1):64-9. 15028074
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
Other Cardiac Phenotype Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. Circ Arrhythm Electrophysiol. 2011 4(6):874-81. 22028457
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 Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block. Circulation. 2012 126(12):1469-77. doi: 10.1161/CIRCULATIONAHA.111.0 22899775
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
p.R367Lc.1100G>T Inherited ArrhythmiaBrSrs28937318SIFT: deleterious
Polyphen: probably damaging
ReportsInherited 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
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