Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000539261 | SCV000628247 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1064 of the RAD50 protein (p.Ile1064Thr). This variant is present in population databases (rs780264599, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 457437). 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. |
| Ambry Genetics | RCV000539261 | SCV000667023 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-01 | criteria provided, single submitter | clinical testing | The p.I1064T variant (also known as c.3191T>C), located in coding exon 21 of the RAD50 gene, results from a T to C substitution at nucleotide position 3191. The isoleucine at codon 1064 is replaced by threonine, an amino acid with 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. |
| Sema4, |
RCV002257789 | SCV002538497 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2022-03-06 | criteria provided, single submitter | curation | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478131 | SCV004220098 | uncertain significance | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in an individual with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/RAD50)). The frequency of this variant in the general population, 0.000004 (1/250930 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |