Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000460333 | SCV000547956 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1013 of the RAD50 protein (p.Ile1013Val). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 408341). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV000460333 | SCV000667074 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-12 | criteria provided, single submitter | clinical testing | The p.I1013V variant (also known as c.3037A>G), located in coding exon 20 of the RAD50 gene, results from a A to G substitution at nucleotide position 3037. This change occurs in the first base pair of coding exon 20. This alteration changes the isoleucine at codon 1013 to valine, an amino acid with highly similar properties. Both the nucleotide and amino acid positions are 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. |