Paralogue Annotation for SCN5A residue 1448

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1448
Reference Amino Acid: I - Isoleucine
Protein Domain: TM Domain 3


Paralogue Variants mapped to SCN5A residue 1448

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AL1461IMyoclonic epilepsy of infancyMedium9 12821740

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.



SCN5AFKGWMDIMYAAVDSRGYEEQPQWEYNLYMY>I<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1478
SCN1AFKGWMDIMYAAVDSRNVELQPKYEESLYMY>L<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1491
SCN2AFKGWMDIMYAAVDSRNVELQPKYEDNLYMY>L<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1481
SCN3AFKGWMDIMYAAVDSRDVKLQPVYEENLYMY>L<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1476
SCN4AFKGWMDIMYAAVDSREKEEQPQYEVNLYMY>L<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1303
SCN7AFNGWITIMNSAIDSVAVNIQPHFEVNIYMY>C<YFINFIIFGVFLPLSMLITVIIDNFNKHKI1201
SCN8AFKGWMDIMYAAVDSRKPDEQPKYEDNIYMY>I<YFVIFIIFGSFFTLNLFIGVIIDNFNQQKK1472
SCN9AFKGWTIIMYAAVDSVNVDKQPKYEYSLYMY>I<YFVVFIIFGSFFTLNLFIGVIIDNFNQQKK1454
SCN10AFKGWMDIMYAAVDSREVNMQPKWEDNVYMY>L<YFVIFIIFGGFFTLNLFVGVIIDNFNQQKK1426
SCN11AFKGWMDIIYAAVDSTEKEQQPEFESNSLGY>I<YFVVFIIFGSFFTLNLFIGVIIDNFNQQQK1316
CACNA1AGEGWPQVLKHSVDATFENQGPSPGYRMEMS>I<FYVVYFVVFPFFFVNIFVALIIITFQEQGD1519
CACNA1BGEGWPMVLKHSVDATYEEQGPSPGYRMELS>I<FYVVYFVVFPFFFVNIFVALIIITFQEQGD1425
CACNA1CFEGWPELLYRSIDSHTEDKGPIYNYRVEIS>I<FFIIYIIIIAFFMMNIFVGFVIVTFQEQGE1174
CACNA1DFEGWPALLYKAIDSNGENIGPIYNHRVEIS>I<FFIIYIIIVAFFMMNIFVGFVIVTFQEQGE1180
CACNA1EGEGWPQVLQHSVDVTEEDRGPSRSNRMEMS>I<FYVVYFVVFPFFFVNIFVALIIITFQEQGD1431
CACNA1FFEGWPALLYKAIDAYAEDHGPIYNYRVEIS>V<FFIVYIIIIAFFMMNIFVGFVIITFRAQGE1145
CACNA1GKDGWVDIMYDGLDAVGVDQQPIMNHNPWML>L<YFISFLLIVAFFVLNMFVGVVVENFHKCRQ1545
CACNA1HKDGWVNIMYDGLDAVGVDQQPVQNHNPWML>L<YFISFLLIVSFFVLNMFVGVVVENFHKCRQ1563
CACNA1IKDGWVNIMYNGLDAVAVDQQPVTNHNPWML>L<YFISFLLIVSFFVLNMFVGVVVENFHKCRQ1439
CACNA1SFEGWPQLLYKAIDSNAEDVGPIYNNRVEMA>I<FFIIYIILIAFFMMNIFVGFVIVTFQEQGE1073
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.I1448Lc.4342A>C Inherited ArrhythmiaBrSSIFT: tolerated
Polyphen: benign
ReportsInherited 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
Unknown Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510
p.I1448Tc.4343T>C Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: benign
ReportsInherited 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