ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.192del (p.Lys64fs)

dbSNP: rs771055189
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV000669061 SCV002576743 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2022-09-23 reviewed by expert panel curation The c.192del (p.Lys64fs) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 3/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD is 0.0001603 in the African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). At least one patient with positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency has been reported with this variant (PMID: 26385305). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting.
Counsyl RCV000669061 SCV000793762 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-08-30 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000669061 SCV001364951 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.192delA (NP_000009.1:p.Lys64AsnfsTer53) [GRCH38: NC_000017.11:g.7220517delA] 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 RCV000669061 SCV001578416 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-01-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys64Asnfs*53) 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 (rs771055189, gnomAD 0.02%). 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: 553583). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000669061 SCV004212637 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-09-03 criteria provided, single submitter clinical testing

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