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 | |
Invitae | RCV001876288 | SCV002262393 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-11-29 | 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). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MFN2 protein function. ClinVar contains an entry for this variant (Variation ID: 933228). This missense change has been observed in individuals with autosomal dominant Charcot-Marie-Tooth disease (PMID: 26801520; Invitae). |