Paralogue Annotation for SCN5A residue 1740

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1740
Reference Amino Acid: G - Glycine
Protein Domain: TM Domain 4


Paralogue Variants mapped to SCN5A residue 1740

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AG1754RDravet syndromeMedium3 22071555
SCN2AG1744RAutism spectrum disorderMedium3 26637798

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.



SCN5AGWDGLLSPILNTGPPYCDPTLPN-S-NGSR>G<D---CGSPAVGILFFTTYIIISFLIVVNMY1767
SCN1AGWDGLLAPILNSKPPDCDPNKVN-PGSSVK>G<D---CGNPSVGIFFFVSYIIISFLVVVNMY1781
SCN2AGWDGLLAPILNSGPPDCDPDKDH-PGSSVK>G<D---CGNPSVGIFFFVSYIIISFLVVVNMY1771
SCN3AGWDGLLAPILNSAPPDCDPDTIH-PGSSVK>G<D---CGNPSVGIFFFVSYIIISFLVVVNMY1766
SCN4AGWDGLLNPILNSGPPDCDPNLEN-PGTSVK>G<D---CGNPSIGICFFCSYIIISFLIVVNMY1593
SCN7AGWDGMLDAIFNSKWSDCDPDKIN-PGTQVR>G<D---CGNPSVGIFYFVSYILISWLIIVNMY1491
SCN8AGWDGLLLPILN-RPPDCSLDKEH-PGSGFK>G<D---CGNPSVGIFFFVSYIIISFLIVVNMY1761
SCN9AGWDGLLAPILNSKPPDCDPKKVH-PGSSVE>G<D---CGNPSVGIFYFVSYIIISFLVVVNMY1744
SCN10AGWDGLLSPILNTGPPYCDPNLPN-S-NGTR>G<D---CGSPAVGIIFFTTYIIISFLIMVNMY1717
SCN11AGWDSLLSPMLRSKES-CN---------SSS>E<N---CHLPGIATSYFVSYIIISFLIVVNMY1599
CACNA1AAWHNIMLSCLSG--KPCDKNSGIL-----T>-<R--ECGN-EFAYFYFVSFIFLCSFLMLNLF1806
CACNA1BAWHEIMLSCLSN--QACDE---Q------A>-<NATECGS-DFAYFYFVSFIFLCSFLMLNLF1704
CACNA1CAWQDIMLACMPG--KKCAPESEP-SNSTEG>E<TP--CGS-SFAVFYFISFYMLCAFLIINLF1471
CACNA1DAWQEIMLACLPG--KLCDPESDY--NPGE->E<YT--CGS-NFAIVYFISFYMLCAFLIINLF1479
CACNA1EAWQEIMLSCLGE--KGCEPDTTAPSGQNEN>-<E--RCGT-DLAYVYFVSFIFFCSFLMLNLF1718
CACNA1FAWQEIMLASLPG--NRCDPESDF--GPGE->E<FT--CGS-NFAIAYFISFFMLCAFLIINLF1436
CACNA1GNWNGIMKDTLRD----CDQEST-----C-->-<----YNT-VISPIYFVSFVLTAQFVLVNVV1846
CACNA1HNWNGIMKDTLRE----CSREDKH----C-->-<LS--YLP-ALSPVYFVTFVLVAQFVLVNVV1855
CACNA1INWNGIMKDTLRD----CTHDERS----C-->-<LS--SLQ-FVSPLYFVSFVLTAQFVLINVV1725
CACNA1SAWQEILLACSYG--KLCDPESDY--APGE->E<YT--CGT-NFAYYYFISFYMLCAFLVINLF1376
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G1740Rc.5218G>A Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002 105(11):1342-7. 11901046
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
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
Inherited ArrhythmiaBrS Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome. Can J Cardiol. 2004 20(4):425-30. 15057319