Paralogue Annotation for SCN5A residue 374

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 374
Reference Amino Acid: W - Tryptophan
Protein Domain: TM Domain 1


Paralogue Variants mapped to SCN5A residue 374

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AW384RDravet syndrome C ?High9 21248271, 23195492
SCN1AW384XMyoclonic epilepsy of infancyHigh9 17347258, 25525159

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.



SCN5AAGENPDHGYTSFDSFAWAFLALFRLMTQDC>W<ERLYQQTLRSAGKIY-MIFFMLVIFLGSFY403
SCN1AAGRNPNYGYTSFDTFSWAFLSLFRLMTQDF>W<ENLYQLTLRAAGKTY-MIFFVLVIFLGSFY413
SCN2AAGRNPNYGYTSFDTFSWAFLSLFRLMTQDF>W<ENLYQLTLRAAGKTY-MIFFVLVIFLGSFY415
SCN3AAGRNPNYGYTSFDTFSWAFLSLFRLMTQDY>W<ENLYQLTLRAAGKTY-MIFFVLVIFLGSFY414
SCN4ATGRNPNYGYTSYDTFSWAFLALFRLMTQDY>W<ENLFQLTLRAAGKTY-MIFFVVIIFLGSFY437
SCN7AAGINPDQGFTNFDSFGWALFALFRLMAQDY>P<EVLYHQILYASGKVY-MIFFVVVSFLFSFY384
SCN8AAGRNPNYGYTSFDTFSWAFLALFRLMTQDY>W<ENLYQLTLRAAGKTY-MIFFVLVIFVGSFY401
SCN9AIGRNPDYGYTSFDTFSWAFLALFRLMTQDY>W<ENLYQQTLRAAGKTY-MIFFVVVIFLGSFY392
SCN10ATSDNPDFNYTSFDSFAWAFLSLFRLMTQDS>W<ERLYQQTLRTSGKIY-MIFFVLVIFLGSFY387
SCN11ATKINPDYNYTNFDNFGWSFLAMFRLMTQDS>W<EKLYQQTLRTTGLYS-VFFFIVVIFLGSFY390
CACNA1AYWEGPNNGITQFDNILFAVLTVFQCITMEG>W<TDLLYNSNDASGNTWNWLYFIPLIIIGSFF350
CACNA1BYWPGPNFGITNFDNILFAILTVFQCITMEG>W<TDILYNTNDAAGNTWNWLYFIPLIIIGSFF346
CACNA1CGWDGPKHGITNFDNFAFAMLTVFQCITMEG>W<TDVLYWVNDAVGRDWPWIYFVTLIIIGSFF395
CACNA1DGWVGPNGGITNFDNFAFAMLTVFQCITMEG>W<TDVLYWVNDAIGWEWPWVYFVSLIILGSFF396
CACNA1EDWIGPNDGITQFDNILFAVLTVFQCITMEG>W<TTVLYNTNDALGATWNWLYFIPLIIIGSFF341
CACNA1FRWPGPNGGITNFDNFFFAMLTVFQCVTMEG>W<TDVLYWMQDAMGYELPWVYFVSLVIFGSFF362
CACNA1GGEHNPFKGAINFDNIGYAWIAIFQVITLEG>W<VDIMYFVMDAHSF-YNFIYFILLIIVGSFF385
CACNA1HGDSNPHNGAINFDNIGYAWIAIFQVITLEG>W<VDIMYYVMDAHSF-YNFIYFILLIIVGSFF409
CACNA1IGSANPHKGAINFDNIGYAWIVIFQVITLEG>W<VEIMYYVMDAHSF-YNFIYFILLIIVGSFF388
CACNA1SGWPGPNHGITHFDNFGFSMLTVYQCITMEG>W<TDVLYWVNDAIGNEWPWIYFVTLILLGSFF324
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.W374Gc.1120T>G Inherited ArrhythmiaBrSrs199473566SIFT: 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