ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.308G>A (p.Gly103Glu) (rs121913600)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536804 SCV000636244 likely pathogenic Charcot-Marie-Tooth disease, type I 2018-05-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 103 of the MPZ protein (p.Gly103Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with severe CMT1 in a single family (PMID: 11445635). It was observed in two affected siblings and was absent in one unaffected sibling. This variant was also reported to be mosaic in the unaffected mother, and presumably arose de novo in this individual. This variant is also known as p.Gly74Glu in the literature. ClinVar contains an entry for this variant (Variation ID: 14187). 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. The observation of one or more missense substitutions at this codon (p.Gly103) in affected individuals suggests that this may be a clinically significant residue (PMID: 20456450). 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.
OMIM RCV000015251 SCV000035510 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2001-07-10 no assertion criteria provided literature only

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