ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.841C>T (p.Arg281Ter)

gnomAD frequency: 0.00002  dbSNP: rs185741664
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725859 SCV000340010 pathogenic not provided 2016-03-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000281372 SCV000656958 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2025-01-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg281*) in the MCCC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). This variant is present in population databases (rs185741664, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with mild biochemical features of 3MCC deficiency (PMID: 22264772, 22642865). ClinVar contains an entry for this variant (Variation ID: 203795). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000281372 SCV002017231 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2021-03-12 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000281372 SCV002813848 likely pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2021-12-02 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003390913 SCV004119922 likely pathogenic MCCC1-related disorder 2023-09-22 criteria provided, single submitter clinical testing The MCCC1 c.841C>T variant is predicted to result in premature protein termination (p.Arg281*). This variant has been documented in one patient diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency and presenting with developmental delay. This patient carried the c.841C>T in the heterozygous state and no second variant was found (Morscher et al. 2012, PMID 22264772). This variant is reported in 0.021% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-182775131-G-A). Nonsense variants in MCCC1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics RCV000281372 SCV004191944 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2024-03-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275513 SCV001460698 pathogenic Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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