Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821234 | SCV000961987 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with methionine at codon 638 of the MRE11 protein (p.Lys638Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine. 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. 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. |
Ambry Genetics | RCV001013674 | SCV001174290 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-19 | criteria provided, single submitter | clinical testing | The p.K638M variant (also known as c.1913A>T), located in coding exon 16 of the MRE11A gene, results from an A to T substitution at nucleotide position 1913. The lysine at codon 638 is replaced by methionine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |