Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131401 | SCV000186377 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-03 | criteria provided, single submitter | clinical testing | The p.M618V variant (also known as c.1852A>G), located in coding exon 15 of the MRE11A gene, results from an A to G substitution at nucleotide position 1852. The methionine at codon 618 is replaced by valine, an amino acid with highly similar properties. In one study, this variant was reported in 1/1313 early-onset breast cancer cases and 0/1123 population controls (Damiola F et al. Breast Cancer Res. 2014 Jun;16(3):R58). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV000508182 | SCV000604247 | uncertain significance | not specified | 2017-02-10 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002228662 | SCV000834144 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 618 of the MRE11 protein (p.Met618Val). This variant is present in population databases (rs375630981, gnomAD 0.004%). This missense change has been observed in individual(s) with breast cancer (PMID: 24894818). ClinVar contains an entry for this variant (Variation ID: 142333). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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, |
RCV002498644 | SCV002812071 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2021-07-06 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477551 | SCV004220920 | uncertain significance | not provided | 2016-04-11 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000023 (3/128832 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 24894818 (2014)). In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer as well as in unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/MRE11A)). 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. |