ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.1771C>T (p.Gln591Ter)

gnomAD frequency: 0.00001  dbSNP: rs1215450873
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564272 SCV000662156 pathogenic Hereditary cancer-predisposing syndrome 2019-10-28 criteria provided, single submitter clinical testing The p.Q591* pathogenic mutation (also known as c.1771C>T), located in coding exon 14 of the MRE11A gene, results from a C to T substitution at nucleotide position 1771. This changes the amino acid from a glutamine to a stop codon within coding exon 14. This alteration has been detected in 0/3030 patients with pancreatic cancer and 1/123136 controls (Hu C et al. JAMA, 2018 06;319:2401-2409). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222551 SCV002500184 likely pathogenic Hereditary breast ovarian cancer syndrome 2022-03-01 criteria provided, single submitter clinical testing Variant summary: MRE11 c.1771C>T (p.Gln591X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4e-06 in 250746 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1771C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV002232642 SCV002509451 pathogenic Ataxia-telangiectasia-like disorder 2021-02-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln591*) in the MRE11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 479737). For these reasons, this variant has been classified as Pathogenic.

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