Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000228619 | SCV000273494 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-02 | criteria provided, single submitter | clinical testing | The p.K50Q variant (also known as c.148A>C), located in coding exon 2 of the RAD50 gene, results from an A to C substitution at nucleotide position 148. The lysine at codon 50 is replaced by glutamine, an amino acid with similar properties. This amino acid position is 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 | RCV000228619 | SCV000289006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 50 of the RAD50 protein (p.Lys50Gln). 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: 230076). 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. |