Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000163460 | SCV000214011 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-19 | criteria provided, single submitter | clinical testing | The p.A419T variant (also known as c.1255G>A), located in coding exon 9 of the RAD50 gene, results from a G to A substitution at nucleotide position 1255. The alanine at codon 419 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved and threonine is the reference amino acid in several 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 | RCV000163460 | SCV000753307 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 419 of the RAD50 protein (p.Ala419Thr). 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: 184246). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs786201357, gnomAD 0.003%). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477592 | SCV004219273 | uncertain significance | not provided | 2023-08-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in individuals with RAD50-related conditions in the published literature. The frequency of this variant in the general population, 0.0000042 (1/235552 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |