ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.1960_1979dup (p.Lys661fs) (rs587781442)

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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 RCV000129354 SCV000184118 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Other strong data supporting pathogenic classification,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Ambry Genetics RCV000219080 SCV000278626 pathogenic Tumor susceptibility linked to germline BAP1 mutations 2015-09-04 criteria provided, single submitter clinical testing
Invitae RCV000129354 SCV000255301 pathogenic Hereditary cancer-predisposing syndrome 2015-06-15 criteria provided, single submitter clinical testing This sequence change inserts 20 nucleotides in exon 18 of the MRE11A mRNA (c.1960_1979dup20), causing a frameshift at codon 661. This creates a premature translational stop signal (p.Lys661Thrfs*45) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature and is not present in population databases, truncating variants in MRE11A are known to be pathogenic (PMID: 10612394, 11371508). ClinVar contains an entry for this variant (RCV000129354). The residues affected by this frameshift belong to the second DNA binding domain of MRE11A protein (PMID: 9845372, 24894818). For these reasons, this variant has been classified as Pathogenic.
Invitae RCV000642448 SCV000764127 pathogenic Ataxia-telangiectasia-like disorder 1 2017-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys661Thrfs*45) in the MRE11 gene. It is expected to result in an absent or disrupted protein product. 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 disease. ClinVar contains an entry for this variant (Variation ID: 141025). Loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). For these reasons, this variant has been classified as Pathogenic.

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