ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1754del (p.Thr585fs) (rs864622617)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203927 SCV000261354 likely pathogenic Multiple endocrine neoplasia, type 1 2015-10-20 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 10 of the MEN1 mRNA (c.1739delC), causing a frameshift at codon 580. This creates a premature translational stop signal in the last exon of the MEN1 mRNA (p.Thr580Argfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated MEN1 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. This frameshift change truncates the functionally conserved NLS2 domain 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). In summary, this is a novel frameshift variant that truncates an important functional domain in MEN1. For these reasons, it has been classified as a Likely Pathogenic.

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