ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.189C>G (p.Phe63Leu) (rs137880635)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523092 SCV000621113 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing The F63L variant in the MEN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F63L variant is not observed in large population cohorts (Lek et al., 2016). The F63L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Although this substitution occurs at a position that is conserved across species, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret F63L as a variant of uncertain significance.
Invitae RCV000559995 SCV000628071 uncertain significance Multiple endocrine neoplasia, type 1 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 63 of the MEN1 protein (p.Phe63Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs137880635, ExAC 0.02%). This variant has not been reported in the literature in individuals with MEN1-related disease. ClinVar contains an entry for this variant (Variation ID: 452316). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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