Paralogue Annotation for SCN5A residue 1357

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1357
Reference Amino Acid: A - Alanine
Protein Domain: TM Domain 3


Paralogue Variants mapped to SCN5A residue 1357

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AA1370PDravet syndrome B ?High9 21248271
SCN10AA1304TPeripheral neuropathy, painfulHigh9 23115331

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.



SCN5ALVGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFGRCINQTEGDL-P-LNYTIVNNKSQCE1385
SCN1ALLGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFYHCINTTTGDR---FDIEDVNNHTDCL1397
SCN2ALLGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFYHCINYTTGEM---FDVSVVNNYSECK1387
SCN3ALVGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFYHCVNMTTGNM---FDISDVNNLSDCQ1385
SCN4ALLGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFYYCINTTTSER---FDISEVNNKSECE1210
SCN7ALIKTTLPTLNVFLVCLMIWLIFSIMGVDLF>A<GRFYECIDPTSGER---FPSSEVMNKSRCE1108
SCN8ALVGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKYHYCFNETSEIR---FEIEDVNNKTECE1377
SCN9ALIGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFYECINTTDGSR---FPASQVPNRSECF1360
SCN10ALVGAIPSIMNVLLVCLIFWLIFSIMGVNLF>A<GKFWRCINYTDGEF-SLVPLSIVNNKSDCK1333
SCN11ALIGAIPAILNVLLVCLIFWLVFCILGVYFF>S<GKFGKCINGTDSVI----NYTIITNKSQCE1227
CACNA1AVVNSLKNVFNILIVYMLFMFIFAVVAVQLF>K<GKFFHCTDESKEFEKDCRGKYLLYEKNEVK1430
CACNA1BVVNSLKNVLNILIVYMLFMFIFAVIAVQLF>K<GKFFYCTDESKELERDCRGQYLDYEKEEVE1336
CACNA1CVFVAIRTIGNIVIVTTLLQFMFACIGVQLF>K<GKLYTCSDSSKQTEAECKGNYITYKDGEVD1082
CACNA1DVFVAIRTIGNIMIVTTLLQFMFACIGVQLF>K<GKFYRCTDEAKSNPEECRGLFILYKDGDVD1088
CACNA1EVVTSLKNVFNILIVYKLFMFIFAVIAVQLF>K<GKFFYCTDSSKDTEKECIGNYVDHEKNKME1342
CACNA1FVFVAIRTIGNIMIVTTLLQFMFACIGVQLF>K<GKFYTCTDEAKHTPQECKGSFLVYPDGDVS1053
CACNA1GLMSSLKPIGNIVVICCAFFIIFGILGVQLF>K<GKFFVCQGED---------TRNITNKSDCA1456
CACNA1HLISSLRPIGNIVLICCAFFIIFGILGVQLF>K<GKFYYCEGPD---------TRNISTKAQCR1474
CACNA1ILISSLKPIGNIVLICCAFFIIFGILGVQLF>K<GKFYHCLGVD---------TRNITNRSDCM1350
CACNA1SMFVAISTIGNIVLVTTLLQFMFACIGVQLF>K<GKFFRCTDLSKMTEEECRGYYYVYKDGDPM981
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.A1357Vc.4070C>T Inherited ArrhythmiaLQTSrs370588133SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. Genet Test Mol Biomarkers. 2013 17(7):553-61. doi: 10.1089/gtmb.2012.0118. 23631430
Inherited ArrhythmiaLQTS Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Am J Hum Genet. 2016 98(5):801-17. doi: 10.1016/j.ajhg.2016.02.024. 27153395