Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000002000 | SCV000458145 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2016-07-28 | criteria provided, single submitter | clinical testing | The MCCC2 c.499T>C (p.Cys167Arg) variant is a missense variant that has been reported in a homozygous state in one individual with 3-methylcrotonyl-CoA carboxylase deficiency (Gallardo et al. 2001). The p.Cys167Arg variant was absent from 100 controls. It is reported at a frequency of 0.00009 in the Latino population of the Exome Aggregation Consortium, but this frequency is based on one allele in a region of good sequence coverage; therefore, the variant is presumed to be rare. Based on the limited evidence, the p.Cys167Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for 3-methylcrotonyl-CoA carboxylase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000002000 | SCV000961815 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-05-01 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with autosomal recessive 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 11170888, 14680978). This variant is present in population databases (rs119103222, gnomAD 0.006%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 167 of the MCCC2 protein (p.Cys167Arg). ClinVar contains an entry for this variant (Variation ID: 1923). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MCCC2 function (PMID: 14680978). 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 MCCC2 protein function. |
Baylor Genetics | RCV000002000 | SCV004194316 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-10-25 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000002000 | SCV000022158 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2001-02-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000002000 | SCV002084288 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2020-12-24 | no assertion criteria provided | clinical testing |