Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498532 | SCV000589719 | likely pathogenic | not provided | 2015-12-18 | criteria provided, single submitter | clinical testing | The S120F variant that is likely pathogenic was identified in the MCCC1 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S120F variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S120F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the biotin carboxylation domain of the MCCC1 protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Invitae | RCV000814269 | SCV000954671 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 120 of the MCCC1 protein (p.Ser120Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 27601257; Invitae). ClinVar contains an entry for this variant (Variation ID: 432047). 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 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. |