Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012617 | SCV001173093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-10 | criteria provided, single submitter | clinical testing | The p.S560N variant (also known as c.1679G>A), located in coding exon 11 of the RAD50 gene, results from a G to A substitution at nucleotide position 1679. The serine at codon 560 is replaced by asparagine, an amino acid with highly similar 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 | RCV001012617 | SCV001540575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-31 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 819769). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 560 of the RAD50 protein (p.Ser560Asn). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478615 | SCV004219289 | uncertain significance | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000008 (2/251144 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |