Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001176420 | SCV001340397 | uncertain significance | Cardiomyopathy | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 785 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 been reported in an individual affected with epilepsy (PMID: 33897349). This variant has been identified in 1/249288 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. |
| Labcorp Genetics |
RCV002558815 | SCV001374814 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 785 of the RYR2 protein (p.Asp785Asn). This variant is present in population databases (rs774486571, gnomAD 0.003%). This missense change has been observed in individual(s) with epilepsy (PMID: 33897349). ClinVar contains an entry for this variant (Variation ID: 918690). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RYR2 protein function with a negative 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. |
| Fulgent Genetics, |
RCV002497615 | SCV002813399 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-10-29 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004006296 | SCV004814643 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia | 2024-02-05 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 785 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 been reported in an individual affected with epilepsy (PMID: 33897349). This variant has been identified in 1/249288 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. |