ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.799-9G>A (rs794728625)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507248 SCV000604212 pathogenic not specified 2016-12-19 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000205749 SCV000781721 pathogenic Multiple endocrine neoplasia, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000182415 SCV000234758 pathogenic not provided 2018-10-11 criteria provided, single submitter clinical testing The c.784-9G>A splice site variant in the MEN1 gene has been previously reported in association with multiple endocrine neoplasia type 1, and has segregated with disease in many families (for examples, see Kishi et al., 1999; Fabbri et al., 2010; Gan et al., 2015). Functional studies show c.784-9G>A creates a new splice acceptor site, leading to aberrant splicing (Kishi et al., 1999). Based on currently available evidence, we consider c.784-9G>A to be pathogenic.
Invitae RCV000205749 SCV000260047 pathogenic Multiple endocrine neoplasia, type 1 2018-08-15 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the MEN1 gene. It does not directly change the encoded amino acid sequence of the MEN1 protein. This variant is not present in population databases (rs794728625, ExAC no frequency). This variant has been reported in many individuals affected with multiple endocrine neoplasia type 1 (MEN1), and segregates with disease in some of the affected families (PMID: 10424788, 10090472, 12050235, 17879353, 22470073). In a study that included 1,336 individuals with MEN1, this intronic change was found in 1.9% of the cases, suggesting that it is a common cause of disease (PMID: 17879353). ClinVar contains an entry for this variant (Variation ID: 200981). This variant is also known as 799-9G>A, 894-9G>A, IVS4-9G>A, 5168G>A, and 5178-9G>A in the literature. Experimental studies using blood and tumor samples from affected individuals have shown that this intronic change generates a new acceptor splice site, resulting in the incorporation of 7 nucleotides from intron 4 into the final mRNA (PMID: 10424788, 10861493, 12050235). This would result in a frameshift, and a premature translational stop signal 9 codons downstream. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000205749 SCV000838456 pathogenic Multiple endocrine neoplasia, type 1 2018-07-02 criteria provided, single submitter clinical testing
OMIM RCV000205749 SCV000038459 pathogenic Multiple endocrine neoplasia, type 1 2002-06-01 no assertion criteria provided literature only

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