Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000809952 | SCV000950136 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2018-10-01 | criteria provided, single submitter | clinical testing | 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has been observed in combination with another MCCC1 variant in an individual affected with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the MCCC1 gene (p.His708Glnfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acids of the MCCC1 protein. |
| Baylor Genetics | RCV000809952 | SCV005060771 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2024-01-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005056583 | SCV005726365 | uncertain significance | not specified | 2024-11-13 | criteria provided, single submitter | clinical testing | Variant summary: MCCC1 c.2123dupA (p.His708GlnfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250162 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2123dupA has been reported in the literature in the presumed compound heterozygous state in at least 1 individual affected with Methylcrotonyl-CoA Carboxylase Deficiency (example, Grunert_2012). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (example, Grunert_2012). The following publication has been ascertained in the context of this evaluation (PMID: 22642865). ClinVar contains an entry for this variant (Variation ID: 654061). Based on the evidence outlined above, the variant was classified as uncertain significance. |