Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794969 | SCV000934407 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2018-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 100 of the PMP22 protein (p.Gly100Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMP22-related disease. 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. This variant disrupts the p.Gly100 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 9585367, 9187667), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Molecular Genetics Laboratory, |
RCV001173924 | SCV001337043 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |