Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001967398 | SCV002206947 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 563 of the MCCC2 protein (p.Met563Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs373922744, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. 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 MCCC2 protein function. 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. |