Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000518242 | SCV000614090 | uncertain significance | not specified | 2016-09-12 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV000790050 | SCV001337444 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV001360038 | SCV001555933 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-12-18 | 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 98 of the MFN2 protein (p.Lys98Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant MFN2-related conditions (PMID: 18957892, 32376792; Invitae). ClinVar contains an entry for this variant (Variation ID: 447723). 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 with a positive predictive value of 95%. 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. |
Inherited Neuropathy Consortium | RCV000790050 | SCV000929440 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |