ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.296T>C (p.Ile99Thr) (rs1571819182)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812847 SCV000953175 pathogenic Charcot-Marie-Tooth disease, type I 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 99 of the MPZ protein (p.Ile99Thr). 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 several individuals affected with Charcot-Marie-Tooth disease, type 1 (PMID: 9888385, 10093067, 26310628) and has been observed to segregate with Charcot-Marie-Tooth disease in a family (PMID: 11080236 ). Experimental studies have shown that this missense change causes retention of the MPZ protein in the endoplasmic reticulum leading to increased protein degradation (PMID: 29687021). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000789473 SCV001336805 pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789473 SCV000928829 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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