Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002534771 | SCV000944021 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2018-09-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RYR2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with valine at codon 3291 of the RYR2 protein (p.Asp3291Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. 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. 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 C65"). |
| Gene |
RCV002462164 | SCV002756773 | likely pathogenic | not provided | 2022-05-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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); Published functional studies suggest reduced response to adrenergic stimulation; however, it is unclear how these study results may translate to a pathogenic role in vivo (Blancard et al., 2021); This variant is associated with the following publications: (PMID: 19926015, 34202968) |