ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.691A>T (p.Ile231Phe)

gnomAD frequency: 0.00001  dbSNP: rs531567604
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002031053 SCV002313893 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-12-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 231 of the MCCC2 protein (p.Ile231Phe). This variant is present in population databases (rs531567604, gnomAD 0.003%). This missense change has been observed in individual(s) with 3-Methylcrotonylglycinuria (PMID: 26589311, 29767664). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1521022). 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%. 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 RCV002031053 SCV004194320 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-01-29 criteria provided, single submitter clinical testing

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