Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003018786 | SCV003314896 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-14 | 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. This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 922 of the RYR2 protein (p.Ser922Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. 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 not expected to disrupt RYR2 protein function. |
| Ambry Genetics | RCV004673765 | SCV005158811 | uncertain significance | Cardiovascular phenotype | 2024-04-04 | criteria provided, single submitter | clinical testing | The p.S922T variant (also known as c.2764T>A), located in coding exon 24 of the RYR2 gene, results from a T to A substitution at nucleotide position 2764. The serine at codon 922 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |