Paralogue Annotation for RYR2 residue 4867

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 4867
Reference Amino Acid: I - Isoleucine
Protein Domain: Transmembrane region

Paralogue Variants mapped to RYR2 residue 4867

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
RYR1I4938TMalignant hyperthermiaHigh9 19191329
RYR1I4938MCentral core diseaseHigh9 14985404

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.I4867Mc.14601T>G Inherited ArrhythmiaCPVTSIFT: deleterious
Polyphen: benign
ReportsInherited ArrhythmiaCPVT Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 106(1):69-74. 12093772
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 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.I4867Vc.14599A>G Inherited ArrhythmiaCPVTSIFT:
ReportsInherited ArrhythmiaCPVT Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes. Heart Rhythm. 2013 10(11):1653-60. doi: 10.1016/j.hrthm.2013.08.022. 23973953