ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.428_467del (p.Gly143fs)

dbSNP: rs758144859
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV000671508 SCV002576773 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2022-09-20 reviewed by expert panel curation The c.428_467del; p.Gly143AlafsTer61 variant in ACADVL results in a frameshift predicted to cause a premature stop codon in biologically relevant exon 6/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). This variant is absent from gnomAD population database v2.1.1 (PM2_Supporting). This variant has also been reported once in a heterozygote patient with Very long chain acyl-coA dehydrogenase deficiency (VLCADD) (PP4, PMID:26385305). The ACADVL Variant Curation Expert Panel VCEP classified the variant as pathogenic based on (PVS1+PM2_supporting, PP4).
GeneDx RCV000480851 SCV000572612 pathogenic not provided 2021-02-12 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26385305)
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000671508 SCV001364959 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.428_467del40 (NP_000009.1:p.Gly143AlafsTer61) [GRCH38: NC_000017.11:g.7221009_7221048del] 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
Invitae RCV000671508 SCV001579730 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-10-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly143Alafs*61) 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 present in population databases (rs758144859, gnomAD 0.0009%). 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: 422995). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000671508 SCV004217013 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-05-23 criteria provided, single submitter clinical testing
Counsyl RCV000671508 SCV000796491 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-12-18 no assertion criteria provided clinical testing

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.