ClinVar Miner

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

dbSNP: rs1571819182
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812847 SCV000953175 pathogenic Charcot-Marie-Tooth disease, type I 2020-12-16 criteria provided, single submitter clinical testing 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 ). For these reasons, this variant has been classified as Pathogenic. 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). This variant is not present in population databases (ExAC no frequency). 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.
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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