ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.1972A>G (p.Thr658Ala)

gnomAD frequency: 0.00004  dbSNP: rs587782756
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132275 SCV000187358 likely benign Hereditary cancer-predisposing syndrome 2020-05-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000524526 SCV000288938 uncertain significance Ataxia-telangiectasia-like disorder 2022-07-09 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 658 of the MRE11 protein (p.Thr658Ala). This variant is present in population databases (rs587782756, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. 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: 142837). 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 alanine 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.
Athena Diagnostics RCV000517173 SCV000614123 uncertain significance not specified 2016-11-16 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000132275 SCV002538413 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-29 criteria provided, single submitter curation

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