ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.332T>C (p.Met111Thr) (rs759808649)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698651 SCV000827331 uncertain significance Charcot-Marie-Tooth disease, type I 2019-12-26 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 111 of the PMP22 protein (p.Met111Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs759808649, ExAC 0.02%). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (PMID: 19259128). 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. 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.
Inherited Neuropathy Consortium RCV000789520 SCV000928876 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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