ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.463C>T (p.Arg155Trp)

gnomAD frequency: 0.00002  dbSNP: rs141030969
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686151 SCV000813655 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 155 of the MCCC2 protein (p.Arg155Trp). This variant is present in population databases (rs141030969, gnomAD 0.009%). This missense change has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16010683, 22642865, 26566957). ClinVar contains an entry for this variant (Variation ID: 566363). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MCCC2 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg155 amino acid residue in MCCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22642865). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000686151 SCV000894360 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-06-07 criteria provided, single submitter clinical testing
GeneDx RCV001567596 SCV001791311 likely pathogenic not provided 2019-11-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31589614, 27601257, 26566957, 16010683, 22642865, 25087612)
Revvity Omics, Revvity RCV000686151 SCV003833932 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2022-03-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000686151 SCV004194335 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-03-06 criteria provided, single submitter clinical testing

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