ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.856_857del (p.Arg286fs)

dbSNP: rs2071269046
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV001200802 SCV004037591 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-09-26 reviewed by expert panel curation The c.856_857del (p.Arg286fs)(NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one individual with this variant was identified by newborn screen, but this information is insufficient to use toward classification (PMID: 26385305). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Suporting (ACADVL VCEP specifications version 1; approved November 9, 2021).
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV001200802 SCV001364967 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.856_857delAG (NP_000009.1:p.Arg286GlyfsTer11) [GRCH38: NC_000017.11:g.7222280_7222281del] 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
Revvity Omics, Revvity RCV001200802 SCV002020552 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2020-09-23 criteria provided, single submitter clinical testing
Invitae RCV001200802 SCV002241260 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg286Glyfs*11) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 932846). For these reasons, this variant has been classified as Pathogenic.

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