Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000175221 | SCV000226666 | pathogenic | not provided | 2013-11-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001231585 | SCV001404113 | pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2019-10-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). This variant has not been reported in the literature in individuals with MCCC1-related conditions. This variant is present in population databases (rs727504001, ExAC 0.002%). This sequence change creates a premature translational stop signal (p.Lys635Asnfs*6) in the MCCC1 gene. It is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509256 | SCV002819771 | likely pathogenic | Methylcrotonyl-CoA carboxylase deficiency | 2022-12-23 | criteria provided, single submitter | clinical testing | Variant summary: MCCC1 c.1905delA (p.Lys635AsnfsX6) 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. Truncations downstream of this position have been associated with 3-methylcrotonyl-CoA carboxylase deficiency in HGMD and are classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4e-06 in 251348 control chromosomes. To our knowledge, no occurrence of c.1905delA 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 pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |