Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489602 | SCV000576773 | uncertain significance | not provided | 2019-05-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ai |
RCV000489602 | SCV002501321 | uncertain significance | not provided | 2022-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003766740 | SCV004632508 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-12-24 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 426356). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (rs532016557, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2566 of the RYR2 protein (p.Arg2566Gln). |