ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1114C>T (p.Gln372Ter)

gnomAD frequency: 0.00005  dbSNP: rs544349961
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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) RCV000723480 SCV000225391 pathogenic not provided 2014-12-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000174145 SCV000611279 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2017-05-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000174145 SCV000775370 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2025-01-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln372*) 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 (rs544349961, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase (MCC) deficiency (PMID: 22642865). ClinVar contains an entry for this variant (Variation ID: 193913). For these reasons, this variant has been classified as Pathogenic.
DASA RCV000174145 SCV002499402 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2022-04-10 criteria provided, single submitter clinical testing The c.1114C>T;p.(Gln372*) variant creates a premature translational stop signal in the MCCC1 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 193913; PMID: 22642865) -PS4. The variant is present at low allele frequencies population databases (rs544349961 – gnomAD 0.0003944%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. The p.(Gln372*) was detected in trans with a pathogenic variant (PMID: 22642865) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Baylor Genetics RCV000174145 SCV004194277 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2024-02-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001275510 SCV004241499 pathogenic Methylcrotonyl-CoA carboxylase deficiency 2023-12-14 criteria provided, single submitter clinical testing Variant summary: MCCC1 c.1114C>T (p.Gln372X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 2.4e-05 in 251408 control chromosomes (gnomAD). c.1114C>T has been reported in the literature in an individuals affected with Methylcrotonyl-CoA Carboxylase Deficiency who was compound heterozygous with another truncating variant (Grunert_2012). The following publication has been ascertained in the context of this evaluation (PMID: 22642865). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001275510 SCV001460695 pathogenic Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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