Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000259066 | SCV000113926 | uncertain significance | not provided | 2015-04-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000653496 | SCV000775376 | pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 439 of the MCCC1 protein (p.Val439Met). This variant is present in population databases (rs398124352, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865, 31901042; Invitae). ClinVar contains an entry for this variant (Variation ID: 95940). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MCCC1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003398679 | SCV004104077 | uncertain significance | MCCC1-related condition | 2023-03-15 | criteria provided, single submitter | clinical testing | The MCCC1 c.1315G>A variant is predicted to result in the amino acid substitution p.Val439Met. This variant has been reported in a compound heterozygous and a homozygous unrelated individual with 3-methylcrotonyl-CoA carboxylase deficiency (Grünert et al 2012. PubMed ID: 22642865; Wu D et al 2019. PubMed ID: 31901042). This variant is reported in 0.0028% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-182756876-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV000653496 | SCV004194261 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2023-09-09 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000653496 | SCV002079098 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2020-12-23 | no assertion criteria provided | clinical testing |