Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000525895 | SCV000636249 | pathogenic | Charcot-Marie-Tooth disease, type I | 2018-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 133 of the MPZ protein (p.Pro133Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Charcot-Marie-Tooth disease (Invitae). 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. The observation of one or more missense substitutions at this codon (p.Pro133Ala and p.Pro133Ser) in affected individuals suggests that this may be a clinically significant residue (PMID: 26310628, 22433810). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000763261 | SCV000893899 | likely pathogenic | Charcot-Marie-Tooth disease type 2I; Charcot-Marie-Tooth disease type 2J; Charcot-Marie-Tooth disease, demyelinating, type 1b; Charcot-Marie-Tooth disease dominant intermediate d; Roussy-Lévy syndrome; Dejerine-Sottas disease; Congenital hypomyelinating neuropathy 1, autosomal recessive | 2018-10-31 | criteria provided, single submitter | clinical testing |