Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002554477 | SCV001230581 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-07-25 | 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 not expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 859492). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 4476 of the RYR2 protein (p.Pro4476Ser). |
| Ambry Genetics | RCV002379595 | SCV002694570 | uncertain significance | Cardiovascular phenotype | 2022-05-05 | criteria provided, single submitter | clinical testing | The p.P4476S variant (also known as c.13426C>T), located in coding exon 92 of the RYR2 gene, results from a C to T substitution at nucleotide position 13426. The proline at codon 4476 is replaced by serine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |