Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000213954 | SCV000279563 | pathogenic | not provided | 2016-10-18 | criteria provided, single submitter | clinical testing | The S149R pathogenic variant in the PMP22 gene has been reported previously as a de novo pathogenic variant in an individual with a clinical diagnosis of Dejerine-Sottas disease (Ohnishi et al., 2000). The S149R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S149R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a conserved position predicted to be within the fourth transmembrane domain of the PMP22 protein (Ohnishi et al., 2000). Missense variants in nearby residues (L147R, G150C/D/R) have been reported in the Human Gene Mutation Database in association with PMP22-related disorders (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function. |
Inherited Neuropathy Consortium | RCV000790160 | SCV000929551 | uncertain significance | Dejerine-Sottas disease | no assertion criteria provided | literature only |