Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000527393 | SCV000628200 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 791 of the RAD50 protein (p.Asp791Ala). This variant is present in population databases (rs758031764, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 457405). |
Ambry Genetics | RCV000527393 | SCV003855380 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-09 | criteria provided, single submitter | clinical testing | The p.D791A variant (also known as c.2372A>C), located in coding exon 14 of the RAD50 gene, results from an A to C substitution at nucleotide position 2372. The aspartic acid at codon 791 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |