Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001904237 | SCV002124152 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 326 of the MFN2 protein (p.Ala326Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1358741). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |