Paralogue Annotation for SCN5A residue 1743

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1743
Reference Amino Acid: G - Glycine
Protein Domain: TM Domain 4


Paralogue Variants mapped to SCN5A residue 1743

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AG1757RDravet syndromeHigh5 27465585

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.



SCN5ASPILNTGPPYCDPTLPN-S-NGSRGD---C>G<SPAVGILFFTTYIIISFLIVVNMYIAIILE1773
SCN1AAPILNSKPPDCDPNKVN-PGSSVKGD---C>G<NPSVGIFFFVSYIIISFLVVVNMYIAVILE1787
SCN2AAPILNSGPPDCDPDKDH-PGSSVKGD---C>G<NPSVGIFFFVSYIIISFLVVVNMYIAVILE1777
SCN3AAPILNSAPPDCDPDTIH-PGSSVKGD---C>G<NPSVGIFFFVSYIIISFLVVVNMYIAVILE1772
SCN4ANPILNSGPPDCDPNLEN-PGTSVKGD---C>G<NPSIGICFFCSYIIISFLIVVNMYIAIILE1599
SCN7ADAIFNSKWSDCDPDKIN-PGTQVRGD---C>G<NPSVGIFYFVSYILISWLIIVNMYIVVVME1497
SCN8ALPILN-RPPDCSLDKEH-PGSGFKGD---C>G<NPSVGIFFFVSYIIISFLIVVNMYIAIILE1767
SCN9AAPILNSKPPDCDPKKVH-PGSSVEGD---C>G<NPSVGIFYFVSYIIISFLVVVNMYIAVILE1750
SCN10ASPILNTGPPYCDPNLPN-S-NGTRGD---C>G<SPAVGIIFFTTYIIISFLIMVNMYIAVILE1723
SCN11ASPMLRSKES-CN---------SSSEN---C>H<LPGIATSYFVSYIIISFLIVVNMYIAVILE1605
CACNA1ALSCLSG--KPCDKNSGIL-----T-R--EC>G<N-EFAYFYFVSFIFLCSFLMLNLFVAVIMD1812
CACNA1BLSCLSN--QACDE---Q------A-NATEC>G<S-DFAYFYFVSFIFLCSFLMLNLFVAVIMD1710
CACNA1CLACMPG--KKCAPESEP-SNSTEGETP--C>G<S-SFAVFYFISFYMLCAFLIINLFVAVIMD1477
CACNA1DLACLPG--KLCDPESDY--NPGE-EYT--C>G<S-NFAIVYFISFYMLCAFLIINLFVAVIMD1485
CACNA1ELSCLGE--KGCEPDTTAPSGQNEN-E--RC>G<T-DLAYVYFVSFIFFCSFLMLNLFVAVIMD1724
CACNA1FLASLPG--NRCDPESDF--GPGE-EFT--C>G<S-NFAIAYFISFFMLCAFLIINLFVAVIMD1442
CACNA1GKDTLRD----CDQEST-----C-------Y>N<T-VISPIYFVSFVLTAQFVLVNVVIAVLMK1852
CACNA1HKDTLRE----CSREDKH----C---LS--Y>L<P-ALSPVYFVTFVLVAQFVLVNVVVAVLMK1861
CACNA1IKDTLRD----CTHDERS----C---LS--S>L<Q-FVSPLYFVSFVLTAQFVLINVVVAVLMK1731
CACNA1SLACSYG--KLCDPESDY--APGE-EYT--C>G<T-NFAYYYFISFYMLCAFLVINLFVAVIMD1382
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G1743Ec.5228G>A Inherited ArrhythmiaBrSSIFT: 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 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 Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF. Anesthesia unmasked Brugada syndrome. Heart Rhythm. 2006 3(9):1074-8. 16945804
p.G1743Rc.5227G>A Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects. Life Sci. 2003 72(21):2391-9. 12639704
Inherited ArrhythmiaBrS A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res. 2004 62(1):53-62. 15023552
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 Spectrum and Prevalence of Mutations Involving BrS1- Through BrS12-Susceptibility Genes in a Cohort of Unrelated Patients Referred for Brugada Syndrome Genetic Testing: Implications for Genetic Testing. J Am Coll Cardiol. 2012 60(15):1410-8. doi: 10.1016/j.jacc.2012.04.037. 22840528
Other Cardiac Phenotype Loss-of-Function SCN5A Mutations Associated with Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture. Circ Arrhythm Electrophysiol. 2015 26111534