ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1303G>A (p.Ala435Thr)

gnomAD frequency: 0.00007  dbSNP: rs142507365
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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 RCV000804238 SCV000944135 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-10-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 435 of the MCCC1 protein (p.Ala435Thr). This variant is present in population databases (rs142507365, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 32746448; Invitae). 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: 649327). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MCCC1 protein function. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001275507 SCV001460692 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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