Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012222 | SCV001172648 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-13 | criteria provided, single submitter | clinical testing | The p.M525R variant (also known as c.1574T>G), located in coding exon 10 of the RAD50 gene, results from a T to G substitution at nucleotide position 1574. The methionine at codon 525 is replaced by arginine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001012222 | SCV004274283 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 819563). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 525 of the RAD50 protein (p.Met525Arg). 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 expected to disrupt RAD50 protein function. 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. |