Paralogue Annotation for SCN5A residue 596

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 596
Reference Amino Acid: D - Aspartate
Protein Domain: Interdomain Linker I-II


Paralogue Variants mapped to SCN5A residue 596

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN2AD649NDravet syndrome Medium2 22029951, 23195492
SCN9AD623NSmall fibre neuropathyMedium2 21698661, 23850641

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.



SCN5A---P--GHALHGKKNSTV------------>D<CNGVVSLLG-AGD----PEAT-SPGSHLLR620
SCN1A---T--SRSSRMLAVFPAN----GKMHSTV>D<CNGVVSLVG-G-P----SVPT-SPVGQLLP669
SCN2A---A--SRASRVLPILPMN----GKMHSAV>D<CNGVVSLVG-G-P----STLT-SA-GQLLP671
SCN3A---A--SMSSRMVPGLPAN----GKMHSTV>D<CNGVVSLVG-G-P----SALT-SPTGQLPP672
SCN4A----------------PAH----GK----->D<CNGSLDTSQ-G-------------------515
SCN7A------------------------------>-<------------------------------
SCN8A---G--SRSSRIFPSLRRS----VKRNSTV>D<CNGVVSLIG-G-P----GSHI---GGRLLP665
SCN9A---A--SRSP---PMLPVN----GKMHSAV>D<CNGVVSLVD-G-R----SALM-LPNGQLLP646
SCN10ALPQP--SNP------D-------------->-<------SRH-G-E----DEHQPPPT-SELA578
SCN11A------------------------------>D<CQKKPQLLE-Q------------------T498
CACNA1A------------------------------>-<------------------------------
CACNA1B------------------------------>-<------------------------------
CACNA1C------------------------------>-<------------------------------
CACNA1D------------------------------>-<------------------------------
CACNA1E------------------------------>-<------------------------------
CACNA1F------------------------------>-<------------------------------
CACNA1G---G--KVYPTVHTSPPPETLKEKALVEVA>A<SSGPPTLTSL-NI----PPGPY-SSMHKLL636
CACNA1H---GTMN-YPTILPSGVGSGKGSTSPGPKG>K<WAGGPPGTGGHGPLSLNSPDPY-EKIPHVV664
CACNA1I------------------------------>T<LAS---------------------------548
CACNA1S------------------------------>-<------------------------------
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.D596Gc.1787A>G Putative Benignrs199473131SIFT: tolerated
Polyphen: probably damaging
ReportsPutative Benign Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Putative Benign 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