ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.274G>A (p.Val92Met) (rs267607245)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519851 SCV000617782 uncertain significance not specified 2017-07-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MPZ gene. The V92M variant has been previously reported in a patient with CMT2 who also had two other MPZ variants, I162M and V92M; analysis of cloned PCR fragments was consistent with all 3 alleles being present on the same allele (in cis) (Boerkoel et al., 2001). The V92M variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V92M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (Y88H, I89N, D90E/H, G93E/A, K96E, E97V) have been reported in the Human Gene Mutation Database in association with CMT (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, the majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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