ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.586T>C (p.Tyr196His)

dbSNP: rs2112329234
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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 RCV002050980 SCV002116985 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2021-06-09 criteria provided, single submitter clinical testing 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. 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 variant has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 196 of the MCCC2 protein (p.Tyr196His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine.

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