Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571115 | SCV000663665 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.Q527R variant (also known as c.1580A>G), located in coding exon 10 of the RAD50 gene, results from an A to G substitution at nucleotide position 1580. The glutamine at codon 527 is replaced by arginine, an amino acid with highly similar properties. This alteration was seen in 0/732 breast cancer patients, 0/189 colorectal cancer patients and 1/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). 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. |
| Invitae | RCV000571115 | SCV000828934 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 527 of the RAD50 protein (p.Gln527Arg). This variant is not present in population databases (gnomAD no frequency). 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: 480425). 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. |
| Fulgent Genetics, |
RCV000764578 | SCV000895669 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478219 | SCV004219284 | uncertain significance | not provided | 2022-09-09 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). 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 deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |