Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151770 | SCV000200188 | uncertain significance | not specified | 2014-04-04 | criteria provided, single submitter | clinical testing | The Ala3442Val variant in RYR2 has not been reported in individuals with cardiom yopathy or in large population studies. Splice prediction tools suggest that thi s variant may create a novel splice site but their accuracy is unknown. Other co mputational predictions do not provide strong support for or against an impact t o the protein. Additional information is needed to fully assess the clinical sig nificance of the Ala3442Val variant. |
| Labcorp Genetics |
RCV002514928 | SCV003273762 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-02-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3442 of the RYR2 protein (p.Ala3442Val). This variant is present in population databases (rs727503403, gnomAD 0.0009%). 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: 165115). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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. |