ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1159T>G (p.Phe387Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003417026 SCV004116031 uncertain significance MCCC2-related disorder 2022-11-23 criteria provided, single submitter clinical testing The MCCC2 c.1159T>G variant is predicted to result in the amino acid substitution p.Phe387Val. This variant was reported along with a known pathogenic MCCC2 variant in an asymptomatic individual with 3-methylcrotonyl-CoA carboxylase deficiency who was identified by newborn screening (Fonseca et al. 2016. PubMed ID: 27601257). We have also observed this variant along with a pathogenic MCCC2 variant in one patient, although no clinical information was provided for that individual (PreventionGenetics internal data). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. Although we suspect this variant may possibly be pathogenic, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003498001 SCV004293741 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-01-09 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This missense change has been observed in individual(s) with clinical features of MCCC2-related conditions (PMID: 27601257). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 387 of the MCCC2 protein (p.Phe387Val).

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