ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1334A>G (p.Tyr445Cys)

gnomAD frequency: 0.00002  dbSNP: rs145475202
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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 RCV002023817 SCV002302567 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2022-02-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 445 of the MCCC2 protein (p.Tyr445Cys). This variant is present in population databases (rs145475202, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of 3 methylcrotonyl-CoA carboxylase deficiency (Invitae). 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. 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.
GeneDx RCV002284508 SCV002574430 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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