ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.402del (p.Phe134fs) (rs397515385)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182436 SCV000234781 pathogenic not provided 2017-04-04 criteria provided, single submitter clinical testing The c.402delC variant in the MEN1 gene has been reported in association with multiple endocrine neoplasia type 1 (Agarwal et al., 1997; Chandrasekharappa et al., 1997; Guru et al., 1998; McKeeby et al., 2001). Haplotype analysis suggests c.402delC may be a founder mutation in the MEN1 gene (Agarwal et al., 1998). This variant causes a frameshift starting with codon Phenylalanine 134, changes this amino acid to a Leucine, and creates a premature Stop codon at position 51 of the new reading frame denoted p.Phe134LeufsX51. The c.402delC variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.402delC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Based on currently available evidence, we consider c.402delC to be pathogenic, and its presence consistent with a risk to develop features of multiple endocrine neoplasia type 1 for this individual.
Invitae RCV000018161 SCV000253969 pathogenic Multiple endocrine neoplasia, type 1 2019-12-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe134Leufs*51) 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 observed in individuals affected with multiple endocrine neoplasia type 1 (PMID: 9103196, 9463336, 9215689). This variant is also known as c.512delC in the literature. ClinVar contains an entry for this variant (Variation ID: 16681). Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491332 SCV000579627 pathogenic Hereditary cancer-predisposing syndrome 2018-11-01 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Athena Diagnostics Inc RCV000182436 SCV000842746 pathogenic not provided 2018-02-06 criteria provided, single submitter clinical testing
OMIM RCV000018161 SCV000038440 pathogenic Multiple endocrine neoplasia, type 1 1997-04-18 no assertion criteria provided literature only

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