Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000805756 | SCV002576761 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-03-14 | reviewed by expert panel | curation | The NM_000018.4(ACADVL):c.552del (p.Ile184fs) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 8/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism ((PVS1; PMIDs 9973285, 11590124). At least one patient with this variant displayed Newborn Screening and follow-up data, which is highly specific for VLCAD. Specifically, a proband with this variant was identified via newborn screening to have C14:1 uM levels of 2.99 and asserted abnormal plasma acylcarnitine levels (PP4; PMID 24503138). This variant has been detected in at least 1 individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This individual is a compound heterozygous for the variant and a pathogenic variant (p.V283A) although the variants are not confirmed in trans. Based on ACADVL VCEP specific guidelines, a total of 0.5 points is awarded for criteria PM3 (PMID 24503138). This variant is absent from gnomAD v2.2.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as 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, PP4_moderate, PM3_supporting, PS2_supporting.) VCEP classification criteria version 2, 10/15/21. |
| Invitae | RCV000805756 | SCV000945724 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2018-12-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). This variant has been observed in combination with another ACADVL variant in an individual affected with VLCAD deficiency (PMID: 24503138). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile184Metfs*33) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. |
| Baylor Genetics | RCV000805756 | SCV004216035 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-10-13 | criteria provided, single submitter | clinical testing |