Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000288396 | SCV000442296 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2017-04-28 | criteria provided, single submitter | clinical testing | The MCCC1 c.640_641delGG (p.Gly214AsnfsTer5) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Gly214AsnfsTer5 variant has been reported in two studies in which it was found in a compound heterozygous state in two siblings with isolated 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Dantas et al. 2005; Grunert et al. 2012). Both of these individuals carried the same variant on the second allele. While both siblings had biochemical profiles of 3-MCC deficiency, they were reportedly asymptomatic at the time of the study and were lost to follow-up (Grunert et al. 2012). Control data are unavailable for the p.Gly214AsnfsTer5 variant, which is also not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Due to the potential impact of frameshift variants and limited evidence from the literature, the p.Gly214AsnfsTer5 variant is classified as a variant of unknown significance but suspicious for pathogenicity for 3-MCC deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Eurofins Ntd Llc |
RCV000592355 | SCV000704862 | pathogenic | not provided | 2017-01-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000288396 | SCV000961203 | pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly214Asnfs*5) in the MCCC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with 3 Methylcrotonyl-CoA carboxylase deficiency (PMID: 16010683). ClinVar contains an entry for this variant (Variation ID: 344312). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000288396 | SCV004194271 | pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2024-03-09 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001275515 | SCV001460700 | pathogenic | Methylcrotonyl-CoA carboxylase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |