Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000560949 | SCV000669663 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.V389L variant (also known as c.1165G>T), located in coding exon 10 of the MRE11A gene, results from a G to T substitution at nucleotide position 1165. The valine at codon 389 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not 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 | RCV001339845 | SCV001533620 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 389 of the MRE11 protein (p.Val389Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). 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: 483628). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |