ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1930G>T (p.Glu644Ter)

gnomAD frequency: 0.00003  dbSNP: rs905321122
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599442 SCV000709817 pathogenic not provided 2017-11-09 criteria provided, single submitter clinical testing The E644X nonsense variant in the MCCC1 gene has been reported previously in association with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Dantas et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay. The E644X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, we interpret E644X to be a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000653488 SCV000775367 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu644*) 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 (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865). ClinVar contains an entry for this variant (Variation ID: 503626). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000653488 SCV002782183 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2021-10-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV000653488 SCV004194265 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2024-03-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV000653488 SCV002079083 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2020-08-06 no assertion criteria provided clinical testing

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