ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.446-2A>C

dbSNP: rs886042035
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000406326 SCV000330871 pathogenic not provided 2018-11-23 criteria provided, single submitter clinical testing The c.446-2A>C splice site variant in the MEN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant destroys the canonical splice acceptor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Based on currently available evidence, we consider c.446-2A>C to be pathogenic and its presence consistent with a diagnosis of multiple endocrine neoplasia type 1
Laboratory of Molecular and Cytogenetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS) RCV003233029 SCV003930408 pathogenic Multiple endocrine neoplasia, type 1 2023-04-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003233029 SCV005845193 pathogenic Multiple endocrine neoplasia, type 1 2025-01-03 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the MEN1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with multiple endocrine neoplasia type 1 (MEN1) syndrome (internal data). ClinVar contains an entry for this variant (Variation ID: 280917). Studies have shown that disruption of this splice site results in skipping of exon 3, and produces a non-functional protein and/or introduces a premature termination codon (internal data). For these reasons, this variant has been classified as Pathogenic.

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