ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1973_1977+28del (rs776641008)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726783 SCV000702996 likely pathogenic not provided 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV000591068 SCV000775369 pathogenic 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2018-04-13 criteria provided, single submitter clinical testing This sequence change removes the last 5 nucleotides of exon 17 and affects a donor splice site in intron 17 of the MCCC1 gene. It is expected to disrupt RNA splicing and/or create a premature translational stop signal, and likely results in an absent or disrupted protein product. This variant is present in population databases (rs776641008, ExAC 0.009%). This variant has not been reported in the literature in individuals with MCCC1-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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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