Paralogue Annotation for RYR2 residue 2474

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 2474
Reference Amino Acid: R - Arginine
Protein Domain: Cytoplasmic region

Paralogue Variants mapped to RYR2 residue 2474

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
RYR1R2508GCentral core diseaseHigh9 16621918, 20142353, 16732084, 26381711
RYR1R2508CCentral core diseaseHigh9 16621918, 19685112, 16732084
RYR1R2508HCentral core diseaseHigh9 16621918, 16732084, 23558838, 26381711

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 RYR2.

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See full Alignment of Paralogues

Known Variants in RYR2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R2474Sc.7422G>C Inherited ArrhythmiaCPVTSIFT: tolerated
Polyphen: probably damaging
ReportsInherited ArrhythmiaCPVT Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001 103(2):196-200. 11208676
Inherited ArrhythmiaCPVT FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell. 2003 113(7):829-40. 12837242
Inherited ArrhythmiaCPVT Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res. 2005 97(11):1173-81. 16239587
Inherited ArrhythmiaCPVT Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest. 2008 118(6):2230-45. 18483626
Inherited ArrhythmiaCPVT Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 106(1):69-74. 12093772
Inherited ArrhythmiaCPVT Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2012 111(6):708-17. doi: 10.1161/CIRCRESAHA.112.273342. 22828895
Inherited ArrhythmiaCPVT New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia. Circ Cardiovasc Genet. 2013 6(5):481-9. doi: 10.1161/CIRCGENETICS.113.000118. 24025405
p.R2474Gc.7420A>G Inherited ArrhythmiaCPVTSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaCPVT Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan. Circ J. 2013 77(7):1705-13. 23595086