Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001968057 | SCV002224875 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2024-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 473 of the MCCC1 protein (p.Leu473Val). This variant is present in population databases (rs565662458, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1441945). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271706 | SCV002556122 | uncertain significance | not specified | 2022-06-23 | criteria provided, single submitter | clinical testing | Variant summary: MCCC1 c.1417C>G (p.Leu473Val) results in a conservative amino acid change located in the biotin carboxylase, C-terminal domain (IPR005482) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 251368 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MCCC1 causing Methylcrotonyl-CoA Carboxylase Deficiency (7.2e-05 vs 0.0042), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1417C>G in individuals affected with Methylcrotonyl-CoA Carboxylase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Revvity Omics, |
RCV001968057 | SCV003810810 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2020-11-20 | criteria provided, single submitter | clinical testing |