Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001036010 | SCV001199353 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2019-01-25 | 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. This sequence change replaces histidine with arginine at codon 12 of the PMP22 protein (p.His12Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. 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 conditions. This variant has been reported to affect PMP22 protein function (PMID: 10915775). This variant disrupts the p.His12 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been observed in individuals with PMP22-related conditions (PMID: 7728152, 26102530, 10078969, 15474367), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. |
| Gene Discovery Core- |
RCV001548774 | SCV001768739 | pathogenic | Charcot-Marie-Tooth disease, type IA | 2020-02-14 | no assertion criteria provided | research | This variant is interpreted as Pathogenic for Charcot-Marie-Tooth disease, type I; Autosomal Dominant. PS2-De novo (both maternity and paternity confirmed) in a patient with the disease and no family history. PM1- Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. PM2- Absent from controls (gnomad). PM5- Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PMID: 7728152). PP2- Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease. PP3- Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). PP5: Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation (PMIDs: 7728152, 10078969, 10915775, 15474367 and 26102530). |