Paralogue Annotation for SCN5A residue 121

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 121
Reference Amino Acid: R - Arginine
Protein Domain: N-terminus


Paralogue Variants mapped to SCN5A residue 121

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AR118SMyoclonic epilepsy of infancyHigh9 18413471
CACNA1FR82QCongenital stationary night blindnessHigh9 25307992
CACNA1FR82XNight blindness, congenital stationary, incompleteHigh9 11281458, 25525159

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.



SCN5ATFI-VLNKGKTIFRFSATNALYVLSPFHPI>R<RAAVKILVHSLFNMLIMCTILTNCVFMAQH151
SCN1ATFI-VLNKGKAIFRFSATSALYILTPFNPL>R<KIAIKILVHSLFSMLIMCTILTNCVFMTMS148
SCN2ATFI-VLNKGKAISRFSATPALYILTPFNPI>R<KLAIKILVHSLFNMLIMCTILTNCVFMTMS149
SCN3ATFI-VMNKGKAIFRFSATSALYILTPLNPV>R<KIAIKILVHSLFSMLIMCTILTNCVFMTLS148
SCN4ATFI-VLNKGKAIFRFSATPALYLLSPFSVV>R<RGAIKVLIHALFSMFIMITILTNCVFMTMS151
SCN7ATFI-VLNKNRTIFRFNAASILCTLSPFNCI>R<RTTIKVLVHPFFQLFILISVLIDCVFMSLT138
SCN8ATFV-VLNRGKTLFRFSATPALYILSPFNLI>R<RIAIKILIHSVFSMIIMCTILTNCVFMTFS152
SCN9ATFI-VLNKGKTIFRFNATPALYMLSPFSPL>R<RISIKILVHSLFSMLIMCTILTNCIFMTMN146
SCN10ATFM-VLNKGRTISRFSATRALWLFSPFNLI>R<RTAIKVSVHSWFSLFITVTILVNCVCMTRT150
SCN11ATFM-VLNRKRTIYRFSAKHALFIFGPFNSI>R<SLAIRVSVHSLFSMFIIGTVIINCVFMATG149
CACNA1AMAL-YNPIPVRQNCLTVNRSLFLFSEDNVV>R<KYAKKITEWPPFEYMILATIIANCIVLALE118
CACNA1BMAL-YNPIPVKQNCFTVNRSLFVFSEDNVV>R<KYAKRITEWPPFEYMILATIIANCIVLALE115
CACNA1CQYG-KPKKQGSTTATRPPRALLCLTLKNPI>R<RACISIVEWKPFEIIILLTIFANCVALAIY144
CACNA1DQYA-KSKKQGNSSNSRPARALFCLSLNNPI>R<RACISIVEWKPFDIFILLAIFANCVALAIY146
CACNA1EMAL-YNPIPVRQNCFTVNRSLFIFGEDNIV>R<KYAKKLIDWPPFEYMILATIIANCIVLALE109
CACNA1FQHS-KHKTVAVASAQRSPRALFCLTLANPL>R<RSCISIVEWKPFDILILLTIFANCVALGVY112
CACNA1GG-SADSEAEGLPYPALAPVVFFYLSQDSRP>R<SWCLRTVCNPWFERISMLVILLNCVTLGMF101
CACNA1HELG-ADEEQRVPYPALAATVFFCLGQTTRP>R<SWCLRLVCNPWFEHVSMLVIMLNCVTLGMF120
CACNA1IL-D-G-ADPHVPHPDLAPIAFFCLRQTTSP>R<NWCIKMVCNPWFECVSMLVILLNCVTLGMY99
CACNA1SRKK-QPKKPVPEILPRPPRALFCLTLENPL>R<KACISIVEWKPFETIILLTIFANCVALAVY71
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R121Qc.362G>A Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
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
p.R121Wc.361C>T Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS The genetic basis of Brugada syndrome: a mutation update. Hum Mutat. 2009 30(9):1256-66. 19606473
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
Other Cardiac Phenotype Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation. Cardiology. 2010 115(4):311-6. 20395683
Inherited ArrhythmiaBrS Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Nav1.5 α-subunits. Cardiovasc Res. 2012 96(1):53-63. 22739120
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