ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1366-2A>G (rs1060499986)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000457794 SCV000541220 likely pathogenic Multiple endocrine neoplasia, type 1 2016-08-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 of the MEN1 gene. It is expected to disrupt RNA splicing and likely results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MEN1-related disease. However, different variants at this position have been reported in a family with hyperparathyroidism (c.1351-2A>C, also known as 1461-2A>C; PMID: 10617276), and a cohort of individuals who underwent diagnostic MEN1 testing (c.1351-2A>T, also known as c.1461-2A>T; PMID: 15670192). This variant is expected to disrupt splicing of the final exon of MEN1, which contains the functionally conserved nuclear localization signal. 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). Several truncating variants in this exon have been reported to be pathogenic (PMID: 15714081). In summary, this is a novel variant that is expected to disrupt an important functional domain of the MEN1 protein. However, without additional functional and/or genetic data for this variant, it has been classified as Likely Pathogenic.

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