ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1593dup (p.Ser532fs)

dbSNP: rs1060499596
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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 RCV000477936 SCV002769760 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2022-09-05 reviewed by expert panel curation The c.1593dup (p.Ser532GlufsTer30) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 16/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 9973285, 11590124). This variant has been detected in at least one individual identified by abnormal newborn screening or presumed positive on newborn screening for very long chain acyl CoA dehydrogenase (VLCAD) deficiency with no reported follow-up plasma acylcarnitine or enzyme activity (PMID: 26385305). To our knowledge, functional assays have not been reported for this variant. 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_Supporting (ClinGen ACADVL VCEP specifications version#1; 09-05-2022).
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000477936 SCV001364936 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1593dupG (NP_000009.1:p.Ser532GlufsTer30) [GRCH38: NC_000017.11:g.7224381dupG] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 26385305. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3
Baylor Genetics RCV000477936 SCV004211842 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-03-28 criteria provided, single submitter clinical testing
Division of Human Genetics, Children's Hospital of Philadelphia RCV000477936 SCV000536845 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2015-05-09 no assertion criteria provided research

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