Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001066303 | SCV001231310 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2019-03-06 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has been observed to be de novo in an individual affected with Charcot-Marie-Tooth disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 38 of the MPZ protein (p.Val38Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |