Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234496 | SCV001407146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 960889). 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. 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. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 517 of the RAD50 protein (p.Thr517Ala). |
| Ambry Genetics | RCV001234496 | SCV002707425 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-23 | criteria provided, single submitter | clinical testing | The p.T517A variant (also known as c.1549A>G), located in coding exon 10 of the RAD50 gene, results from an A to G substitution at nucleotide position 1549. The threonine at codon 517 is replaced by alanine, an amino acid with 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. |