Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688067 | SCV000815664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs754840961, gnomAD 0.0009%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 567871). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 544 of the RAD50 protein (p.Asp544Gly). |
Ambry Genetics | RCV000688067 | SCV003855407 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | The p.D544G variant (also known as c.1631A>G), located in coding exon 10 of the RAD50 gene, results from an A to G substitution at nucleotide position 1631. The aspartic acid at codon 544 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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. |