Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001226208 | SCV002538667 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2024-02-27 | reviewed by expert panel | curation | The NM_000018.4(ACADVL): c.480C>G (p.Tyr160Ter) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 7/20 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 v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature either in a patient with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency or ACADVL associated disease or in functional studies. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive 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 version 1; approved November 9, 2021). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting. This variant was originally curated November 29, 2021 and the recurated classification was approved by the expert panel on February 27, 2024. |
Invitae | RCV001226208 | SCV001398512 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-06-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr160*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. ClinVar contains an entry for this variant (Variation ID: 953854). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |