ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.578G>A (p.Arg193His)

gnomAD frequency: 0.00001  dbSNP: rs535519604
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001221718 SCV001393778 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 193 of the MCCC2 protein (p.Arg193His). This variant is present in population databases (rs535519604, gnomAD 0.003%). This missense change has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16835865). ClinVar contains an entry for this variant (Variation ID: 950084). 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 not expected to disrupt MCCC2 protein function with a negative predictive value of 80%. This variant disrupts the p.Arg193 amino acid residue in MCCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11181649, 31730530; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Baylor Genetics RCV001221718 SCV004194375 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-04-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV001221718 SCV002084292 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2020-05-22 no assertion criteria provided clinical testing

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