ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1930G>T (p.Glu644Ter) (rs905321122)

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Total submissions: 2
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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.
Invitae RCV000653488 SCV000775367 pathogenic 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2017-11-03 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. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with another MCCC1 variant in a single family affected with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865). Loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). For these reasons, this variant has been classified as Pathogenic.

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