Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164273 | SCV000214898 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-13 | criteria provided, single submitter | clinical testing | The p.A177V variant (also known as c.530C>T), located in coding exon 5 of the MRE11A gene, results from a C to T substitution at nucleotide position 530. The alanine at codon 177 is replaced by valine, an amino acid with similar properties. 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. |
| Invitae | RCV000701788 | SCV000830607 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 177 of the MRE11 protein (p.Ala177Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs773766504, ExAC 0.01%). 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: 184931). 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 disruptive. 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. |