Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203827 | SCV001375005 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 656 of the RAD50 protein (p.Arg656Leu). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 935272). |
| Ambry Genetics | RCV001203827 | SCV002721260 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-03 | criteria provided, single submitter | clinical testing | The p.R656L variant (also known as c.1967G>T), located in coding exon 12 of the RAD50 gene, results from a G to T substitution at nucleotide position 1967. The arginine at codon 656 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |