Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Human Genetics and Genomic Medicine, |
RCV001201342 | SCV001372229 | uncertain significance | Charcot-Marie-Tooth disease type 2A2 | 2020-05-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001876288 | SCV002262393 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2024-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 307 of the MFN2 protein (p.Lys307Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant Charcot-Marie-Tooth disease (PMID: 26801520; internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 933228). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MFN2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |