ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.249_252del (p.Ile85fs) (rs587776841)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491114 SCV000579632 pathogenic Hereditary cancer-predisposing syndrome 2018-02-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000182434 SCV000234779 pathogenic not provided 2018-07-16 criteria provided, single submitter clinical testing The c.249_252delGTCT variant in the MEN1 gene has been reported previously in association with multiple endocrine neoplasia type 1 (for examples, see Poncin et al., 1999; Abe et al., 2000; Tham et al., 2007; de Laat et al., 2014). Lemos et al. (2008) reported a frequency of 4.5% for this variant in individuals with MEN1. The c.249_252delGTCT deletion causes a frameshift starting with codon Isoleucine 85, changes this amino acid to a Serine residue and creates a premature Stop codon at position 33 of the new reading frame, denoted p.Ile85SerfsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider c.249_252delGTCT to be pathogenic.
Invitae RCV000206170 SCV000260440 pathogenic Multiple endocrine neoplasia, type 1 2018-08-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile85Serfs*33) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in many individuals affected with multiple endocrine neoplasia type 1 (PMID: 9103196, 15635078, 17879353, 9215690, 24915123, 17623761). It estimated to be the causative mutation in approximately 5% of all families affected with multiple endocrine neoplasia type 1. ClinVar contains an entry for this variant (Variation ID: 16693). Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000206170 SCV000711456 pathogenic Multiple endocrine neoplasia, type 1 2016-06-21 criteria provided, single submitter clinical testing The p.Ile85fs variant in MEN1 has been reported in multiple individuals with mul tiple endocrine neoplasia type 1 and segregated with disease in affected relativ es (Lemmens 1997, Lemos 2008). It was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino ac id sequence beginning at codon 85 and leads to a premature termination codon 33 amino acids downstream. Heterozygous loss-of-function is an established disease mechanism in multiple endocrine neoplasia type 1. In summary, this variant meets our criteria to be classified as pathogenic for multiple endocrine neoplasia ty pe 1 in an autosomal dominant manner.
OMIM RCV000206170 SCV000038437 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only
OMIM RCV000018173 SCV000038452 pathogenic Lipoma, somatic 1998-03-04 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.