ClinGen Dosage Sensitivity Curation Page
RYR2
- Curation Status: Complete
- id: ISCA-34476
- Date last evaluated: 2015-11-05
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about RYR2 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/6262
- OMIM: https://omim.org/entry/180902
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1116/?term=RYR2%5Bgenesymbol%5D
- ClinGen Haploinsufficiency Score: 0
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 1.0
- Haploinsufficiency score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Haploinsufficiency phenotype comments:
The RYR2 gene encodes the cardiac ryanodine receptor that regulates contraction by the intracellular release of calcium and plays and essential rolein excitation-contraction in the heart (PMID: 24743769) . Pathogenic changes that result in gain-of-function of the RYR2 gene have reported in individuals with several types of tachyarrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT), catecholaminergic idiopathic ventricular fibrillation, atrial fibrillation and a structurally normal heart (Napolitano et al., 2014). Loss of function variants have not been associated with RYR2-related disorders. An in-frame deletion of exon 3 has been reported in patients with CPVT and other arrhythmias, however the pathogenetic mechanism has not been well defined (PMID: 24743769).
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity