Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000691743 | SCV000819533 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-10-31 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the MCCC2 mRNA. It is expected to extend the length of the MCCC2 protein by 3 additional amino acid residues. This variant is present in population databases (rs751970792, gnomAD 0.007%). This protein extension has been observed in individual(s) with 3 Methylcrotonyl-CoA carboxylase deficiency (PMID: 16010683, 22642865; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 570791). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001271415 | SCV004029650 | likely pathogenic | Methylcrotonyl-CoA carboxylase deficiency | 2025-04-21 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.1690T>C (p.X564GlnextX3) changes the termination codon and is predicted to lead to an extended protein with three additional amino acids added to the normal C-terminus. MCCC2 c.1690T>C (p.X564GlnextX3) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 2.8e-05 in 251414 control chromosomes. c.1690T>C has been observed in individual(s) affected with pathognomic clinical and metabolic features of Methylcrotonyl-CoA Carboxylase Deficiency (example: Dantas_2005 overlapping with Grunert_2012 and internal data). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16010683, 22642865). ClinVar contains an entry for this variant (Variation ID: 570791). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Natera, |
RCV001271415 | SCV001452541 | uncertain significance | Methylcrotonyl-CoA carboxylase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV004751665 | SCV005360469 | uncertain significance | MCCC2-related disorder | 2024-06-14 | no assertion criteria provided | clinical testing | The MCCC2 c.1690T>C variant is predicted to result in extension of the open reading frame (p.*564Glnext*3). This variant is predicted to abolish the stop codon and lead to the extension of the protein by 3 amino acids (p.*564Glnext*3). This variant has been reported in the heterozygous state in two patients. A second variant was not identified in the MCCC2 gene of either patient, though no RNA was identified from the second allele in one of the patients, suggesting the presence of an additional variant not detectable via the methodology used by the researchers (Dantas et al. 2005. PubMed ID: 16010683; Grünert et al. 2012. PubMed ID: 22642865). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |