ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.2024T>C (p.Met675Thr)

gnomAD frequency: 0.00001  dbSNP: rs1173614760
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573180 SCV000662195 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-30 criteria provided, single submitter clinical testing The p.M675T variant (also known as c.2024T>C), located in coding exon 18 of the MRE11A gene, results from a T to C substitution at nucleotide position 2024. The methionine at codon 675 is replaced by threonine, an amino acid with 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 RCV001051828 SCV001216006 uncertain significance Ataxia-telangiectasia-like disorder 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 675 of the MRE11 protein (p.Met675Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. 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: 479773). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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