ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1366_*820del (p.Val456fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694224 SCV000822658 pathogenic Multiple endocrine neoplasia, type 1 2018-06-23 criteria provided, single submitter clinical testing This variant is a partial deletion of the genomic region encompassing part of exon 10 (c.1562_*1546del) of the MEN1 gene. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. While this particular variant has not been reported in the literature, larger deletions encompassing exon 10 have been observed in individuals affected with multiple endocrine neoplasia (PMID: 17623761, 28818680, 29036195), and truncating variants in MEN1 are known to be pathogenic (PMID: 17853334, 12112656). This deletion removes the functionally conserved nuclear localization signal of the MEN1 protein. Experimental studies have shown that disruption of this region abrogates the ability of MEN1 to bind DNA, regulate target gene expression, and inhibit cell proliferation (PMID: 15331604, 16449969). For these reasons, this variant has been classified as Pathogenic.

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