Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002720254 | SCV002991564 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2023-02-04 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 540 of the MCCC1 protein (p.Ser540Asn). This variant is present in population databases (rs376408733, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MCCC1-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 not expected to disrupt MCCC1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |