Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564516 | SCV000662133 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-14 | criteria provided, single submitter | clinical testing | The p.R402T variant (also known as c.1205G>C), located in coding exon 10 of the MRE11A gene, results from a G to C substitution at nucleotide position 1205. The arginine at codon 402 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. |
| Invitae | RCV002232397 | SCV002509513 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with threonine at codon 402 of the MRE11 protein (p.Arg402Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs778211645, ExAC 0.009%). This variant has not been reported in the literature in individuals with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 479718). 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: "Possibly 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. |