ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1594C>T (p.Arg532Ter) (rs104894261)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491431 SCV000579759 pathogenic Hereditary cancer-predisposing syndrome 2014-11-19 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)
GeneDx RCV000182423 SCV000234768 pathogenic not provided 2017-09-13 criteria provided, single submitter clinical testing The R527X nonsense variant in the MEN1 gene has been reported previously in association with multiple endocrine neoplasia type 1 (for examples, see Chandrasekharappa et al., 1997; Guru et al., 1998; Teh et al., 1998; Hasani-Ranjbar et al., 2014; Kong et al., 2016). This variant is predicted to cause loss of normal protein function through protein truncation. The R527X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Based on currently available evidence, we consider R527X to be pathogenic.
Genome Sciences Centre,British Columbia Cancer Agency RCV000515522 SCV000611142 likely pathogenic Metastatic pancreatic neuroendocrine tumours 2017-11-01 no assertion criteria provided research
Invitae RCV000018168 SCV000813224 pathogenic Multiple endocrine neoplasia, type 1 2018-09-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Arg527*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 84 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with multiple endocrine neoplasia type I syndrome (MEN1) and MEN1-related disease (PMID: 9103196, 9709921, 22470073,29036195, 25309785, 27846313) and segregates with disease in a MEN1 family (PMID: 24218143). This variant is also known as c.1594C>T (p.Arg532X) and c.1689C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 16688). A different truncation (p.Gln554*) that lies downstream of this variant has been determined to be pathogenic (PMID: 11578300, 17853334, 15331604, 16449969). This suggests that deletion of this region of the MEN1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018168 SCV000038447 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only

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