Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166758 | SCV000217570 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-14 | criteria provided, single submitter | clinical testing | The p.L427S variant (also known as c.1280T>C), located in coding exon 11 of the MRE11A gene, results from a T to C substitution at nucleotide position 1280. The leucine at codon 427 is replaced by serine, an amino acid with dissimilar 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 | RCV002228973 | SCV000547405 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-08-03 | 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 427 of the MRE11 protein (p.Leu427Ser). This variant is present in population databases (rs786203449, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 187070). 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: "Benign"; 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. |