Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003154012 | SCV001555121 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1061 of the RYR2 protein (p.Gly1061Ala). This variant is present in population databases (rs373083911, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051243). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR2 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001751698 | SCV002007247 | uncertain significance | not provided | 2021-04-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 920259; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; 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) |
Ai |
RCV001751698 | SCV002502112 | uncertain significance | not provided | 2022-03-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002322312 | SCV002608099 | uncertain significance | Cardiovascular phenotype | 2022-09-29 | criteria provided, single submitter | clinical testing | The p.G1061A variant (also known as c.3182G>C), located in coding exon 27 of the RYR2 gene, results from a G to C substitution at nucleotide position 3182. The glycine at codon 1061 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly 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. |
All of Us Research Program, |
RCV004005263 | SCV004833819 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia | 2023-08-15 | criteria provided, single submitter | clinical testing |