Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001323885 | SCV001514820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-07 | 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: 1023781). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs754508700, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 785 of the RAD50 protein (p.Ala785Val). |
Ambry Genetics | RCV001323885 | SCV002733132 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | The p.A785V variant (also known as c.2354C>T), located in coding exon 14 of the RAD50 gene, results from a C to T substitution at nucleotide position 2354. The alanine at codon 785 is replaced by valine, an amino acid with similar properties. This amino acid position is highly 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 this alteration remains unclear. |