Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703465 | SCV000832365 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2019-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with proline at codon 159 of the PMP22 protein (p.Arg159Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. 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. A different missense substitution at this codon (p.Arg159Cys) has been reported in an individual affected with Charcot-Marie-Tooth disease, type 1E (PMID: 21337347). 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. |
| Genesis Genome Database | RCV000703465 | SCV000999585 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2019-08-14 | no assertion criteria provided | research | |
| Genesis Genome Database | RCV000857017 | SCV000999586 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |