Paralogue Annotation for SCN5A residue 1632

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1632
Reference Amino Acid: R - Arginine
Protein Domain: TM Domain 4


Paralogue Variants mapped to SCN5A residue 1632

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AR1645QMyoclonic epilepsy of infancyHigh7 17347258
CACNA1AR1668WHemiplegic migraine with cerebellar signsHigh7 11439943, 18437043
CACNA1SR1242GNormokalaemic periodic paralysisHigh7 24240197
SCN4AR1457HCongenital myasthenic syndromeHigh7 25707578, 25707578
SCN1AR1645PDravet syndromeHigh7 26096185
SCN1AR1645XMyoclonic epilepsy of infancyHigh7 14738421

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------------KYFFSPTLFRVIRLARIG>R<ILRLIRGAKGIRTLLFALMMSLPALFNIGL1662
SCN1A------------KYFVSPTLFRVIRLARIG>R<ILRLIKGAKGIRTLLFALMMSLPALFNIGL1675
SCN2A------------KYFVSPTLFRVIRLARIG>R<ILRLIKGAKGIRTLLFALMMSLPALFNIGL1665
SCN3A------------KYFVSPTLFRVIRLARIG>R<ILRLIKGAKGIRTLLFALMMSLPALFNIGL1660
SCN4A------------KYFVSPTLFRVIRLARIG>R<VLRLIRGAKGIRTLLFALMMSLPALFNIGL1487
SCN7A------------SYLVPPSLVQLILLSRII>H<MLRLGKGPKVFHNLMLPLMLSLPALLNIIL1385
SCN8A------------KYFVSPTLFRVIRLARIG>R<ILRLIKGAKGIRTLLFALMMSLPALFNIGL1656
SCN9A------------TYFVSPTLFRVIRLARIG>R<ILRLVKGAKGIRTLLFALMMSLPALFNIGL1638
SCN10A-----------LQSYFSPTLFRVIRLARIG>R<ILRLIRAAKGIRTLLFALMMSLPALFNIGL1612
SCN11A-----------EHIPFPPTLFRIVRLARIG>R<ILRLVRAARGIRTLLFALMMSLPSLFNIGL1502
CACNA1A--------------FINLSFLRLFRA---A>R<LIKLLRQGYTIRILLWTFVQSFKALPYVCL1697
CACNA1B------------NNFINLSFLRLFRA---A>R<LIKLLRQGYTIRILLWTFVQSFKALPYVCL1605
CACNA1C---CSPSMNAEENSRISITFFRLFRV---M>R<LVKLLSRGEGIRTLLWTFIKSFQALPYVAL1365
CACNA1DPVPTATPGNSEESNRISITFFRLFRV---M>R<LVKLLSRGEGIRTLLWTFIKSFQALPYVAL1375
CACNA1E-----------NTSGFNMSFLKLFRA---A>R<LIKLLRQGYTIRILLWTFVQSFKALPYVCL1612
CACNA1F---E----SSEDSSRISITFFRLFRV---M>R<LVKLLSKGEGIRTLLWTFIKSFQALPYVAL1332
CACNA1G-----------ASLPINPTIIRIMRVLRIA>R<VLKLLKMAVGMRALLDTVMQALPQVGNLGL1748
CACNA1H-----------AALPINPTIIRIMRVLRIA>R<VLKLLKMATGMRALLDTVVQALPQVGNLGL1754
CACNA1I-----------AALPINPTIIRIMRVLRIA>R<VLKLLKMATGMRALLDTVVQALPQVGNLGL1624
CACNA1SLGGGCGNVDPDESARISSAFFRLFRV---M>R<LIKLLSRAEGVRTLLWTFIKSFQALPYVAL1272
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R1632Hc.4895G>A Other Cardiac PhenotypeSIFT: deleterious
Polyphen: probably damaging
ReportsOther Cardiac Phenotype Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003 112(7):1019-28. 14523039
Other Cardiac Phenotype Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. J Cardiovasc Electrophysiol. 2010 21(5):564-73. 20384651
Other Cardiac Phenotype Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010 5(6):e10985. 20539757
p.R1632Cc.4894C>T Inherited ArrhythmiaBrSSIFT:
Polyphen:
ReportsInherited ArrhythmiaBrS Enhanced fast-inactivated state stability of cardiac sodium channels by a novel voltage sensor SCN5A mutation, R1632C, as a cause of atypical Brugada syndrome. Heart Rhythm. 2015 12(11):2296-304. doi: 10.1016/j.hrthm.2015.05.032. 26031372
Inherited ArrhythmiaBrS An R1632C variant in the SCN5A gene causing Brugada syndrome. Mol Med Rep. 2016 13(6):4677-80. doi: 10.3892/mmr.2016.5100. 27082542
p.Arg1632Cysc.4894C>T UnknownSIFT:
Polyphen: