ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.161C>G (p.Ser54Cys) (rs1571820092)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001224441 SCV001396633 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-06-17 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 54 of the MPZ protein (p.Ser54Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with severe Charcot-Marie-Tooth disease (PMID: 12090401, 10093067, 25025039); in one of these individuals the variant was reported to be de novo. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Ser54 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 10533074), which suggests that this may be a clinically significant amino acid residue. 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.
Inherited Neuropathy Consortium RCV000789437 SCV000928792 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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