Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000524514 | SCV000254851 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 473 of the MRE11 protein (p.Leu473Ser). This variant is present in population databases (rs771843497, gnomAD 0.03%). This missense change has been observed in individual(s) with a personal or family history of breast cancer (PMID: 27783279). ClinVar contains an entry for this variant (Variation ID: 216608). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV000199015 | SCV000273945 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-07 | criteria provided, single submitter | clinical testing | The p.L473S variant (also known as c.1418T>C), located in coding exon 12 of the MRE11A gene, results from a T to C substitution at nucleotide position 1418. The leucine at codon 473 is replaced by serine, an amino acid with dissimilar properties. In one study of 235 Korean patients with hereditary breast cancer, who had previously had negative BRCA1/2 genetic testing, this variant was observed in 1/470 alleles (Kim H et al. Breast Cancer Res. Treat. 2017 Jan;161:95-102). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003462334 | SCV004193877 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2023-01-05 | criteria provided, single submitter | clinical testing |