Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000989692 | SCV002538669 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-02-22 | reviewed by expert panel | curation | The c199A>T (p.Lys67Ter) variant in ACADVL is a nonsense variant 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 variant has been identified in at least one individual identified by newborn screen for very long chain acyl CoA dehydrogenase (VLCAD) deficiency without an additional ACADVL variant identified or assertion of follow-up plasma acylcarnitines (PMID: 26385305). This variant is absent from gnomAD v2.1.1 (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. VCEP specifications v2.0; Approved on 08/12/2021. |
| ARUP Laboratories, |
RCV000989692 | SCV000883336 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-08-22 | criteria provided, single submitter | clinical testing | The ACADVL c.199A>T; p.Lys67Ter variant (rs765432568) is reported in the literature in a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency (Miller 2015). This variant is reported in ClinVar (Variation ID: 617952), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Miller MJ et al. Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Mol Genet Metab. 2015 Nov;116(3):139-45. |
| Mendelics | RCV000989692 | SCV001140228 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Wong Mito Lab, |
RCV000989692 | SCV001364952 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.199A>T (NP_000009.1:p.Lys67Ter) [GRCH38: NC_000017.11:g.7220524A>T] 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 | RCV000989692 | SCV001591974 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys67*) 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 premature translational stop signal has been observed in individual(s) with clinical features of ACADVL-related disorders (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 617952). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000989692 | SCV004215070 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-08-02 | criteria provided, single submitter | clinical testing |