ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.341T>C (p.Ile114Thr) (rs267607241)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541724 SCV000636247 uncertain significance Charcot-Marie-Tooth disease, type I 2017-08-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 114 of the MPZ protein (p.Ile114Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (CMT) (PMID: 26310628). This variant was also reported to arise de novo in an individual affected with Dejerine-Sottas syndrome, but 2 additional nearby de novo missense changes were identified in this individual, making it difficult to determine the impact of this variant in isolation. This variant is also known as Ile(85)Thr in the literature. ClinVar contains an entry for this variant (Variation ID: 14180). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, this variant has uncertain impact on MPZ function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Inherited Neuropathy Consortium RCV000789491 SCV000928847 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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