ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.266del (p.Pro89fs)

dbSNP: rs771808680
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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 RCV000667604 SCV002538690 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2021-11-04 reviewed by expert panel curation The c.266del variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 4/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The variant has been identified in at least one individual identified by abnormal newborn screening results suggestive of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency without an additional ACADVL variant identified or follow-up plasma acylcarnitines (PMID: 26385305). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00005437 in East Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant. 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 (ACADVL VCEP specifications v2.0; Approved on 12/14/2021).
Counsyl RCV000667604 SCV000792082 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-06-21 criteria provided, single submitter clinical testing
Invitae RCV000667604 SCV000820589 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2021-08-31 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000667604 SCV001364953 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.266delC (NP_000009.1:p.Pro89HisfsTer28) [GRCH38: NC_000017.11:g.7220665del] 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

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