Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000002000 | SCV000458145 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-07-22 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000002000 | SCV000961815 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-05-01 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 167 of the MCCC2 protein (p.Cys167Arg). This variant is present in population databases (rs119103222, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 11170888, 14680978). ClinVar contains an entry for this variant (Variation ID: 1923). 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 MCCC2 protein function. Experimental studies have shown that this missense change affects MCCC2 function (PMID: 14680978). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000002000 | SCV004194316 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-12-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689401 | SCV005185016 | likely pathogenic | Methylcrotonyl-CoA carboxylase deficiency | 2024-05-31 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.499T>C (p.Cys167Arg) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, N-terminal domain (IPR011762) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251476 control chromosomes. c.499T>C has been reported in the literature in at least one homozygous individual affected with Methylcrotonyl-CoA Carboxylase Deficiency (Desviat_2003, Gallardo_2001). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in almost complete loss of MCC activity in MCCB-deficient fibroblasts (0.3% of normal activity) (Desviat_2003). The following publications have been ascertained in the context of this evaluation (PMID: 14680978, 11170888). ClinVar contains an entry for this variant (Variation ID: 1923). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV000002000 | SCV005666596 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-06-04 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000002000 | SCV000022158 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2001-02-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV000002000 | SCV002084288 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2020-12-24 | no assertion criteria provided | clinical testing |