Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689214 | SCV000816854 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-16 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 568759). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 463 of the RAD50 protein (p.Glu463Asp). This variant is present in population databases (rs528351466, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. |
Ambry Genetics | RCV000689214 | SCV001171632 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-27 | criteria provided, single submitter | clinical testing | The p.E463D variant (also known as c.1389A>T), located in coding exon 9 of the RAD50 gene, results from an A to T substitution at nucleotide position 1389. The glutamic acid at codon 463 is replaced by aspartic acid, an amino acid with highly 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. |