Total submissions: 3
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, |
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 |