Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001552197 | SCV001772846 | likely pathogenic | not provided | 2020-11-11 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; A different missense change at this residue (P133A) has been reported in ClinVar (ClinVar SCV000830284.1 ); This variant is associated with the following publications: (PMID: 22433810) |
Invitae | RCV002535802 | SCV003284890 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2022-02-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 637337). This missense change has been observed in individuals with hereditary motor and sensory neuropathy (PMID: 22433810). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 133 of the MPZ protein (p.Pro133Ser). 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. 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 variant disrupts the p.Pro133 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26310628; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
Inherited Neuropathy Consortium | RCV000789457 | SCV000928813 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |