Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000467180 | SCV000548017 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 408377). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs769987307, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 605 of the RAD50 protein (p.Glu605Asp). 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 | RCV000467180 | SCV001173859 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-02-26 | criteria provided, single submitter | clinical testing | The p.E605D variant (also known as c.1815G>C), located in coding exon 12 of the RAD50 gene, results from a G to C substitution at nucleotide position 1815. The glutamic acid at codon 605 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly 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 p.E605D remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477956 | SCV004219293 | uncertain significance | not provided | 2023-08-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/250312 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. |