ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.783+1G>C (rs794728652)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000126 SCV001156567 pathogenic Multiple endocrine neoplasia, type 1 2018-12-09 criteria provided, single submitter clinical testing The MEN1 c.783+1G>C variant, also known as 893+1G>C, is reported in the literature in individuals affected with multiple endocrine neoplasia type 1 (Poncin 1999). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 4, which is likely to disrupt gene function. Additionally, other variants at this nucleotide (c.783+1G>A; c.783+1G>T) have been reported in individuals with multiple endocrine neoplasia type 1 and are considered pathogenic (Giraud 1998, Morelli 2000, Nunes 2014). Based on available information, the c.783+1G>C variant is considered to be pathogenic. References: Giraud S et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet. 1998 Aug;63(2):455-67. Morelli A et al. MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1. Eur J Endocrinol. 2000 Feb;142(2):131-7. Nunes VS et al. Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening. Pituitary. 2014 Feb;17(1):30-7. Poncin J et al. Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Hum Mutat. 1999;13(1):54-60.
Invitae RCV001000126 SCV001230503 pathogenic Multiple endocrine neoplasia, type 1 2019-01-29 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the MEN1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with multiple endocrine neoplasia type 1 (PMID: 9888389, 22666734, 9683585). This splice site is also known as 893+1G and IVS4+1G in the literature. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). For these reasons, this variant has been classified as Pathogenic.

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