Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222267 | SCV000277390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-14 | criteria provided, single submitter | clinical testing | The p.Q479R variant (also known as c.1436A>G), located in coding exon 9 of the RAD50 gene, results from an A to G substitution at nucleotide position 1436. The glutamine at codon 479 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved, and arginine is the reference amino acid in several 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 | RCV000222267 | SCV002149055 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 233085). This sequence change replaces glutamine with arginine at codon 479 of the RAD50 protein (p.Gln479Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. |