Paralogue Annotation for RYR2 residue 4497

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 4497
Reference Amino Acid: R - Arginine
Protein Domain: Transmembrane region

Paralogue Variants mapped to RYR2 residue 4497

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
RYR1R4558QCentral core diseaseHigh9 17226826, 25637381, 26332594

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.R4497Cc.13489C>T Inherited ArrhythmiaCPVTSIFT: deleterious
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 FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. Biochem J. 2009 419(2):273-8. 19226252
Inherited ArrhythmiaCPVT Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation. Cardiovasc Res. 2010 87(1):50-9. 20080988
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