Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000692342 | SCV000820159 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 350 of the RAD50 protein (p.Gln350Arg). This variant is present in population databases (rs751434866, gnomAD 0.006%). 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: 571246). 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. |
| Ambry Genetics | RCV000692342 | SCV001178105 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-28 | criteria provided, single submitter | clinical testing | The p.Q350R variant (also known as c.1049A>G), located in coding exon 7 of the RAD50 gene, results from an A to G substitution at nucleotide position 1049. The glutamine at codon 350 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. 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. |