Paralogue Annotation for SCN5A residue 1660

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1660
Reference Amino Acid: I - Isoleucine
Protein Domain: TM Domain 4


Paralogue Variants mapped to SCN5A residue 1660

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CACNA1AV1696IHemiplegic migraineMedium9 11439943, 22549042
CACNA1AV1696FHemipl. migraine/alternating hemipl. of childhoodMedium9 18498393
SCN1AI1673TDravet syndrome C ?High9 21248271
SCN1AI1673SGeneralised epilepsy with febrile seizures plusHigh9 26339958

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.



SCN5AIGRILRLIRGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYSIFGMANFAYVKW-----E1685
SCN1AIGRILRLIKGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYAIFGMSNFAYVKR-----E1698
SCN2AIGRILRLIKGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYAIFGMSNFAYVKR-----E1688
SCN3AIGRILRLIKGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYAIFGMSNFAYVKK-----E1683
SCN4AIGRVLRLIRGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYSIFGMSNFAYVKK-----E1510
SCN7AIIHMLRLGKGPKVFHNLMLPLMLSLPALLN>I<ILLIFLVMFIYAVFGMYNFAYVKK-----E1408
SCN8AIGRILRLIKGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIFSIFGMSNFAYVKH-----E1679
SCN9AIGRILRLVKGAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYAIFGMSNFAYVKK-----E1661
SCN10AIGRILRLIRAAKGIRTLLFALMMSLPALFN>I<GLLLFLVMFIYSIFGMSSFPHVRW-----E1635
SCN11AIGRILRLVRAARGIRTLLFALMMSLPSLFN>I<GLLLFLIMFIYAILGMNWFSKVNP-----E1525
CACNA1A-ARLIKLLRQGYTIRILLWTFVQSFKALPY>V<CLLIAMLFFIYAIIGMQVFGNIGIDVEDED1725
CACNA1B-ARLIKLLRQGYTIRILLWTFVQSFKALPY>V<CLLIAMLFFIYAIIGMQVFGNIALDD---D1630
CACNA1C-MRLVKLLSRGEGIRTLLWTFIKSFQALPY>V<ALLIVMLFFIYAVIGMQVFGKIALND---T1390
CACNA1D-MRLVKLLSRGEGIRTLLWTFIKSFQALPY>V<ALLIAMLFFIYAVIGMQMFGKVAMRD---N1400
CACNA1E-ARLIKLLRQGYTIRILLWTFVQSFKALPY>V<CLLIAMLFFIYAIIGMQVFGNIKLDE---E1637
CACNA1F-MRLVKLLSKGEGIRTLLWTFIKSFQALPY>V<ALLIAMIFFIYAVIGMQMFGKVALQD---G1357
CACNA1GIARVLKLLKMAVGMRALLDTVMQALPQVGN>L<GLLFMLLFFIFAALGVELFGDLECDET---1773
CACNA1HIARVLKLLKMATGMRALLDTVVQALPQVGN>L<GLLFMLLFFIYAALGVELFGRLECSED---1779
CACNA1IIARVLKLLKMATGMRALLDTVVQALPQVGN>L<GLLFMLLFFIYAALGVELFGKLVCNDE---1649
CACNA1S-MRLIKLLSRAEGVRTLLWTFIKSFQALPY>V<ALLIVMLFFIYAVIGMQMFGKIALVD---G1297
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.I1660Vc.4978A>G Inherited ArrhythmiaLQTS,BrSrs199473625SIFT: deleterious
Polyphen: possibly damaging
ReportsInherited ArrhythmiaLQTS Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944
Inherited ArrhythmiaBrS Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome. Circulation. 2006 114(19):2026-33. 17075016
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 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
Inherited ArrhythmiaLQTS Sodium channelopathies: do we really understand what's going on? J Cardiovasc Electrophysiol. 2011 22(5):590-3. doi: 10.1111/j.1540-8167.2010.01892.x 20812931