Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000687820 | SCV000815408 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1296 of the RAD50 protein (p.Cys1296Ser). 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: 567665). 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 expected to disrupt RAD50 protein function with a positive 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 | RCV003465563 | SCV004207377 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-07-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000687820 | SCV005159426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-14 | criteria provided, single submitter | clinical testing | The p.C1296S variant (also known as c.3886T>A), located in coding exon 25 of the RAD50 gene, results from a T to A substitution at nucleotide position 3886. The cysteine at codon 1296 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |