ClinVar Miner

Submissions for variant NM_130799.2(MEN1):c.1174del (p.Glu392fs) (rs386134247)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255795 SCV000321884 likely pathogenic not provided 2017-03-30 criteria provided, single submitter clinical testing The c.1174delG variant has been reported previously (as 1280delG) in association with multiple endocrine neoplasia type 1 (Agarwal et al., 1997). The c.1174delG variant causes a frameshift starting with codon Glutamic acid 392, changes this amino acid to a Serine residue and creates a premature Stop codon at position 53 of the new reading frame, denoted p.Glu392SerfsX53. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1174delG variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Based on currently available evidence, c.1174delG is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.
Department of Laboratory Medicine,Soonchunhyang University Seoul Hospital RCV000714231 SCV000834125 pathogenic Multiple endocrine neoplasia, type 1 2018-01-23 criteria provided, single submitter clinical testing
Invitae RCV000714231 SCV001400770 pathogenic Multiple endocrine neoplasia, type 1 2019-11-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Glu392Serfs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 219 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9215689). This variant is also known as 1280delG in the literature. ClinVar contains an entry for this variant (Variation ID: 265238). This variant disrupts the C-terminus of the MEN1 protein. Other variant(s) that disrupt this region (p.Lys559Glufs*38) have been determined to be pathogenic (PMID: 10090472, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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