ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.134A>G (p.Glu45Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796726 SCV000936251 likely pathogenic Multiple endocrine neoplasia, type 1 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 45 of the MEN1 protein (p.Glu45Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with disease in a family affected with multiple endocrine neoplasia 1 (MEN1) (PMID: 9832038, 10395230). In addition, this variant has been observed in multiple unrelated individuals affected with MEN1 or hyperparathyroidism (PMID: 9832038, 11216636, 29036195, 19350420, 22187299, 19461164). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Glu45Val and p.Glu45Asp) in affected individuals suggests that this may be a clinically significant residue (PMID: 21266030, 19461164, 9709922). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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