Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001960389 | SCV002223706 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-06-03 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. 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 MCCC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1442910). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 361 of the MCCC2 protein (p.Arg361Gln). |
Prevention |
RCV003401941 | SCV004112512 | uncertain significance | MCCC2-related disorder | 2023-02-08 | criteria provided, single submitter | clinical testing | The MCCC2 c.1082G>A variant is predicted to result in the amino acid substitution p.Arg361Gln. This variant was reported in a study of individual affected with inborn errors of metabolism (Supplementary Table 5 in Adhikari et al. 2020. PubMed ID: 32778825). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |