Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000653487 | SCV000775366 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 553 of the MCCC1 protein (p.Met553Lys). This variant is present in population databases (rs774055789, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of MCCC1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 542945). 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. 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. |
Natera, |
RCV000653487 | SCV001456488 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2020-01-24 | no assertion criteria provided | clinical testing |