Paralogue Annotation for SCN5A residue 1325

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1325
Reference Amino Acid: N - Asparagine
Protein Domain: TM Domain 3


Paralogue Variants mapped to SCN5A residue 1325

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AN1338TDravet syndromeHigh9 24901346, 25356970, 26795593

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.



SCN5AEMGPIKSLRTLRALRPLRALSRFEGMRVVV>N<ALVGAIPSIMNVLLVCLIFWLIFSIMGVNL1355
SCN1AELGAIKSLRTLRALRPLRALSRFEGMRVVV>N<ALLGAIPSIMNVLLVCLIFWLIFSIMGVNL1368
SCN2AELGAIKSLRTLRALRPLRALSRFEGMRVVV>N<ALLGAIPSIMNVLLVCLIFWLIFSIMGVNL1358
SCN3AELGAIKSLRTLRALRPLRALSRFEGMRVVV>N<ALVGAIPSIMNVLLVCLIFWLIFSIMGVNL1356
SCN4AELGPIKSLRTLRALRPLRALSRFEGMRVVV>N<ALLGAIPSIMNVLLVCLIFWLIFSIMGVNL1181
SCN7AE---LKPLISMKFLRPLRVLSQFERMKVVV>R<ALIKTTLPTLNVFLVCLMIWLIFSIMGVDL1079
SCN8AELGAIKSLRTLRALRPLRALSRFEGMRVVV>N<ALVGAIPSIMNVLLVCLIFWLIFSIMGVNL1348
SCN9ADLGPIKSLRTLRALRPLRALSRFEGMRVVV>N<ALIGAIPSIMNVLLVCLIFWLIFSIMGVNL1331
SCN10AEVAPIKALRTLRALRPLRALSRFEGMRVVV>D<ALVGAIPSIMNVLLVCLIFWLIFSIMGVNL1302
SCN11A-LMELKSFRTLRALRPLRALSQFEGMKVVV>N<ALIGAIPAILNVLLVCLIFWLVFCILGVYF1199
CACNA1ADINTIKSLRVLRVLRPLKTIKRLPKLKAVF>D<CVVNSLKNVFNILIVYMLFMFIFAVVAVQL1398
CACNA1BDINTIKSLRVLRVLRPLKTIKRLPKLKAVF>D<CVVNSLKNVLNILIVYMLFMFIFAVIAVQL1304
CACNA1CAINVVKILRVLRVLRPLRAINRAKGLKHVV>Q<CVFVAIRTIGNIVIVTTLLQFMFACIGVQL1050
CACNA1DAISVVKILRVLRVLRPLRAINRAKGLKHVV>Q<CVFVAIRTIGNIMIVTTLLQFMFACIGVQL1056
CACNA1EDIKTIKSLRVLRVLRPLKTIKRLPKLKAVF>D<CVVTSLKNVFNILIVYKLFMFIFAVIAVQL1310
CACNA1FAISVVKILRVLRVLRPLRAINRAKGLKHVV>Q<CVFVAIRTIGNIMIVTTLLQFMFACIGVQL1021
CACNA1GILGMLRVLRLLRTLRPLRVISRAQGLKLVV>E<TLMSSLKPIGNIVVICCAFFIIFGILGVQL1433
CACNA1HILGVLRVLRLLRTLRPLRVISRAPGLKLVV>E<TLISSLRPIGNIVLICCAFFIIFGILGVQL1451
CACNA1IILGVLRVLRLLRTLRPLRVISRAPGLKLVV>E<TLISSLKPIGNIVLICCAFFIIFGILGVQL1327
CACNA1SAISVVKILRVLRVLRPLRAINRAKGLKHVV>Q<CMFVAISTIGNIVLVTTLLQFMFACIGVQL949
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.N1325Sc.3974A>G Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 4(9):1603-7. 8541846
Other Cardiac Phenotype Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res. 2004 61(2):256-67. 14736542
Inherited ArrhythmiaLQTS Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476
Inherited ArrhythmiaLQTS Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
Inherited ArrhythmiaLQTS Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085
Inherited ArrhythmiaLQTS Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte apoptosis, cardiac fibrosis and contractile dysfunction in mice. Int J Cardiol. 2011 147(2):239-45. 19762097
Inherited ArrhythmiaLQTS Multiple mechanisms of Na+ channel--linked long-QT syndrome. Circ Res. 1996 78(5):916-24. 8620612
Inherited ArrhythmiaLQTS Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc Natl Acad Sci U S A. 1996 93(23):13200-5. 8917568