ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.35C>T (p.Pro12Leu) (rs794728614)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538512 SCV000628081 likely pathogenic Multiple endocrine neoplasia, type 1 2017-07-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 12 of the MEN1 protein (p.Pro12Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals from 2 families affected with multiple endocrine neoplasia type 1 (PMID: 9215689, Invitae). Experimental studies have shown that this missense change reduces MEN1 protein stability, interferes with its interaction with the RPA2 protein and affects MEN1 ability to inhibit JunD-mediated transcriptional activation (PMID: 21819486, 22090276, 12509449, 21264250, 15254225). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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