Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570865 | SCV000666997 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-23 | criteria provided, single submitter | clinical testing | The p.R763C variant (also known as c.2287C>T), located in coding exon 14 of the RAD50 gene, results from a C to T substitution at nucleotide position 2287. The arginine at codon 763 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.R763C remains unclear. |
Invitae | RCV000570865 | SCV000753384 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 763 of the RAD50 protein (p.Arg763Cys). This variant is present in population databases (rs369996457, gnomAD 0.007%). 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: 482085). 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. |
Cancer Genomics Group, |
RCV001030508 | SCV001193708 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-05-01 | criteria provided, single submitter | research |