ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1667C>T (p.Thr556Ile)

dbSNP: rs1049171546
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001998721 SCV002276022 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 556 of the MCCC2 protein (p.Thr556Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 25381946; Invitae). ClinVar contains an entry for this variant (Variation ID: 1483322). 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 with a positive predictive value of 95%. 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.

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