Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131520 | SCV000186514 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-10 | criteria provided, single submitter | clinical testing | The p.M658V variant (also known as c.1972A>G) is located in coding exon 13 of the RAD50 gene. This alteration results from an A to G substitution at nucleotide position 1972. The methionine at codon 658 is replaced by valine, an amino acid with highly similar properties. Based on protein sequence alignment, this amino acid position is 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. |
| Invitae | RCV000131520 | SCV000289023 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 658 of the RAD50 protein (p.Met658Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 142417). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |