ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1339C>T (p.Gln447Ter) (rs794728654)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182456 SCV000234801 pathogenic not provided 2019-01-15 criteria provided, single submitter clinical testing The Q442X nonsense mutation in the MEN1 gene has been reported previously in association with multiple endocrine neoplasia, type 1 (Shimizu et al., 1997; Pieterman et al., 2012). The premature stop codon results in the loss of the last 169 amino acids and the resulting truncated protein is predicted to have lost normal protein function. The presence of Q442X is consistent with a diagnosis of multiple endocrine neoplasia, type 1. The variant is found in MEN1 panel(s).
Invitae RCV000812559 SCV000952877 pathogenic Multiple endocrine neoplasia, type 1 2019-11-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Gln442*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 169 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with multiple endocrine neoplasia type 1 (PMID: 9439676, 22470073, 25824098). This variant is also known as c.1339C>T and p.Gln447X in the literature. ClinVar contains an entry for this variant (Variation ID: 201016). This variant disrupts the C-terminus of the MEN1 protein. Other variant(s) that disrupt this region (p.Arg516Glyfs*43) have been determined to be pathogenic (PMID: 9215689, 12112656, 17879353, 23321498). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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