Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486402 | SCV000571987 | likely pathogenic | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | The Q360E variant in the MFN2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q360E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q360E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In addition, this substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (T356A, T356S, K357N, H361Y, T362M, T362R, R364W, R364P, and R364Q) have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth disease or MFN2-related neuropathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, Q360E is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| Labcorp Genetics |
RCV001856863 | SCV002176115 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-04-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth (PMID: 28660751; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 422500). 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. This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 360 of the MFN2 protein (p.Gln360Glu). This variant is not present in population databases (gnomAD no frequency). |
| Genesis Genome Database | RCV000857101 | SCV000999675 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |