Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219674 | SCV000273167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-14 | criteria provided, single submitter | clinical testing | The p.V296I variant (also known as c.886G>A) is located in coding exon 7 of the RAD50 gene. The valine at codon 296 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 7. This amino acid position is highly 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 acceptor 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. |
| Invitae | RCV000219674 | SCV000827678 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 296 of the RAD50 protein (p.Val296Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 229823). 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 disruptive. 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. |