Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000712317 | SCV000842783 | likely pathogenic | not provided | 2017-11-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000462311 | SCV000552939 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2016-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 137 of the MPZ protein (p.Gly137Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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 (PMID: 8664899, 11545686, 26310628). ClinVar contains an entry for this variant (Variation ID: 14173). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Different missense substitutions at this codon (p.Gly137Asp, p.Gly137Ala) have been reported in individuals affected with Charcot-Marie-Tooth disease, but the clinical significance of these variants is uncertain (PMID: 21326314, 24053775, 26310628). In summary, this variant is a rare missense change that has been reported in several affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000015236 | SCV000035495 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 1996-01-01 | no assertion criteria provided | literature only |