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 | 2022-08-23 | 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). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 |