ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.984C>G (p.Tyr328Ter) (rs750904332)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521767 SCV000616774 pathogenic not provided 2017-07-12 criteria provided, single submitter clinical testing The Y323X nonsense variant in the MEN1 gene has been reported previously in association with multiple endocrine neoplasia (Agarwal et al., 1997; Pack et al., 1998; Park et al., 2003; Tso et al., 2003). This variant was found to be apparently de novo in a patient referred for MEN1 testing at GeneDx. The Y323X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This 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 Y323X to be pathogenic, and its presence consistent with a risk to develop features of multiple endocrine neoplasia type 1 for this individual.
Invitae RCV000632110 SCV000753214 pathogenic Multiple endocrine neoplasia, type 1 2018-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr323*) 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 individuals affected with multiple endocrine neoplasia type 1 (PMID: 9215689). ClinVar contains an entry for this variant (Variation ID: 449058). A different variant (c.969C>A) giving rise to the same protein effect observed here (p.Tyr323*) has been reported in individuals affected with multiple endocrine neoplasia (PMID: 12791038, 22026581, 25309785). 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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