Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000572264 | SCV000666994 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-20 | criteria provided, single submitter | clinical testing | The p.R87L variant (also known as c.260G>T), located in coding exon 3 of the RAD50 gene, results from a G to T substitution at nucleotide position 260. The arginine at codon 87 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not 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. |
| Invitae | RCV000572264 | SCV000935008 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 87 of the RAD50 protein (p.Arg87Leu). This variant is present in population databases (rs374561375, gnomAD 0.004%). 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: 482082). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD50 protein function with a negative predictive value of 80%. 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. |
| Baylor Genetics | RCV003459333 | SCV004207371 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-07-11 | criteria provided, single submitter | clinical testing |