Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000431787 | SCV000536513 | uncertain significance | not provided | 2022-12-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign in association with a RYR2-related disorder to our knowledge; Not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28404607) |
Invitae | RCV003103760 | SCV001221339 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-01-18 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001182765 | SCV001348327 | uncertain significance | Cardiomyopathy | 2023-03-21 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 1121 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has been identified in 6/280628 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Mayo Clinic Laboratories, |
RCV000431787 | SCV002541780 | uncertain significance | not provided | 2021-06-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002323667 | SCV002607272 | uncertain significance | Cardiovascular phenotype | 2021-06-18 | criteria provided, single submitter | clinical testing | The p.G1121R variant (also known as c.3361G>C), located in coding exon 28 of the RYR2 gene, results from a G to C substitution at nucleotide position 3361. The glycine at codon 1121 is replaced by arginine, an amino acid with dissimilar properties. This variant was detected in an exome cohort, but clinical details were not provided (Landstrom AP et al. Circ Arrhythm Electrophysiol, 2017 Apr;10:[Epub ahead of print]). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |