Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000153469 | SCV000229160 | pathogenic | not provided | 2013-11-21 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000153469 | SCV000680700 | pathogenic | not provided | 2017-12-06 | criteria provided, single submitter | clinical testing | The c.137-2 A>G splice site variant in the MCCC1 gene has been previously reported as homozygous in an asymptomatic individual with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Stadler et al., 2006). It has also been reported in an assymptomatic infant with positive newborn screening for 3-MCC deficiency in whom a second variant was not identified by sequencing (Morscher et al., 2012). This pathogenic variant destroys the canonical splice acceptor site in intron 2, and is expected to cause abnormal gene splicing. The c.137-2 A>G variant is not observed in large population cohorts (Lek et al., 2016). In summary, we interpret c.137-2 A>G to be a pathogenic variant. |
Invitae | RCV001850097 | SCV002311767 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 of the MCCC1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16835865, 22264772). ClinVar contains an entry for this variant (Variation ID: 167274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Fulgent Genetics, |
RCV001850097 | SCV002792992 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2022-04-21 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001850097 | SCV004194280 | pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2023-06-09 | criteria provided, single submitter | clinical testing |