Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory, |
RCV000790165 | SCV001337033 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV001873226 | SCV002266125 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2022-04-01 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 637835). This missense change has been observed in individuals with PMP22-related conditions (PMID: 21194947, 32376792; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 131 of the PMP22 protein (p.Ser131Cys). |
| Concord Molecular Medicine Laboratory, |
RCV003325975 | SCV004032123 | likely pathogenic | Charcot-Marie-Tooth disease, type IA | 2023-08-23 | criteria provided, single submitter | clinical testing | This variant was detected in a patient with abnormal nerve conduction study with a family history of Charcot-Marie-Tooth (CMT) disease. This variant has been reported to segregate with autosomal dominant CMT with variable phenotypes including mild form of CMT with intermediate nerve conduction, HNPP (PMID: 21194947) and DSS (in house data) in multiple individuals in two unrelated families. The variant is not present in control population (gnomAD). In silico analysis by REVEL suggests this variant to be damaging (REVEL:0.652). ClinVar contains an entry for this variant (Variation ID: 637835), with conflicting interpretation (likely pathogenic/variant of uncertain significance). The current evidence allows a classification of the variant as Likely pathogenic (ACMG criteria: PP1_strong, PM2_supporting, PP3). |
| Inherited Neuropathy Consortium | RCV000790165 | SCV000929556 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |