ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1261C>T (p.Arg421Trp)

gnomAD frequency: 0.00001  dbSNP: rs764744442
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000524927 SCV000656948 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 421 of the MCCC1 protein (p.Arg421Trp). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 30626930; 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: 476391). 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 MCCC1 protein function. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000524927 SCV002779597 uncertain significance 3-methylcrotonyl-CoA carboxylase 1 deficiency 2022-04-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275508 SCV001460693 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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