Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003103767 | SCV000541677 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-11-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000520735 | SCV000616859 | uncertain significance | not provided | 2017-10-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the RYR2 gene. The V2933G variant has not been published as pathogenic or been reported as benign to our knowledge. The V2933G variant is observed in 25/30660 (0.08%) alleles from individuals of South Asian ancesty in large population cohorts (Lek et al., 2016). The V2933G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. The V2933G variant is 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). Nevertheless, this substitution occurs at a position where only amino acids with similar properties to valine (V) are tolerated across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Color Diagnostics, |
RCV001186329 | SCV001352722 | uncertain significance | Cardiomyopathy | 2023-06-01 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with glycine at codon 2933 of the RYR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 38/279924 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. |
| Ambry Genetics | RCV002374739 | SCV002687881 | likely benign | Cardiovascular phenotype | 2021-06-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |