ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.103_112dup (p.Arg38fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV002286685 SCV002576752 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2022-03-08 reviewed by expert panel curation The NM_000018.4: c.103_112dup10 (p.Arg38ProfsTer24) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 2/20 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 2 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency identified by increased C14:1 levels by newborn screen and one of these individuals had an acylcarnitine analysis consistent with VLCAD deficiency (PP4_moderate; PMID: 29519241, 29768383). One of these individuals was homozygous for the variant (PM3_supporting; PMID: 29768383). This variant is absent from gnomAD v2.1.1 (PM2_supporting). In summary, this variant meets the criteria to be classified as 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, PP4_moderate, PM3_supporting, PM2_supporting (VCEP specifications v2.0, approved on 09/16/2021).
Labcorp Genetics (formerly Invitae), Labcorp RCV002286685 SCV004538948 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-04-09 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg38Profs*24) 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 premature translational stop signal has been observed in individual(s) with VLCAD deficiency (PMID: 29519241, 29768383). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1707706).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.