Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000772952 | SCV000906334 | uncertain significance | Cardiomyopathy | 2023-09-25 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 2318 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 been reported in one individual affected with long QT syndrome, who also carried a disease-causing variant in the KCNH2 gene (PMID: 36269083). This variant has also been detected in one individual affected with Brugada syndrome (PMID: 30847666). This variant has been identified in 2/249140 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. |
Invitae | RCV002534044 | SCV002308840 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-01-28 | 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: 628482). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 30847666). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2318 of the RYR2 protein (p.Asn2318Asp). |