ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1077+1G>A (rs140989450)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520772 SCV000616633 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing The c.1077+1 G>A splice site variant in the ACADVL gene destroys the canonical splice donor site in intron 10. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although the c.1077+1 G>A variant has not been previously reported to our knowledge, it is interpreted to be a pathogenic variant.
Counsyl RCV000666633 SCV000790956 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-04-17 criteria provided, single submitter clinical testing
Invitae RCV000666633 SCV001227842 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-04-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the ACADVL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed to be homozygous in or in combination with another ACADVL variant in individuals affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 30194637, 25338548). ClinVar contains an entry for this variant (Variation ID: 448981). 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 ACADVL are known to be pathogenic (PMID: 9973285, 11590124). For these reasons, this variant has been classified as Pathogenic.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000666633 SCV001364974 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1077+1G>A (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7222866G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3

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