ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.303G>T (p.Trp101Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001215918 SCV001387687 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-05-06 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 101 of the MPZ protein (p.Trp101Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MPZ-related conditions. 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: "Benign"; Align-GVGD: "Class C45"). A different variant (c.303G>C) giving rise to the same protein effect observed here (p.Trp101Cys) has been determined to be pathogenic (PMID: 7550231). This suggests that this variant is also likely to be causative of disease. 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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