Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000525582 | SCV000636246 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2017-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 112 of the MPZ protein (p.Ile112Thr). 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: 9452099, 21256749, 26310628, 9888385). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789483 | SCV000928839 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |