Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000693564 | SCV004037584 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-09-26 | reviewed by expert panel | curation | The NM_000018.4(ACADVL):c.809del (p.Pro270GlnfsTer6) variant in ACADVL is a frameshift variant predicted cause a premature stop codon in biologically-relevant-exon 9/20 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). 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_Suporting (ACADVL VCEP specifications version 1; approved November 9, 2021). |
Invitae | RCV000693564 | SCV000821437 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2018-04-23 | criteria provided, single submitter | clinical testing | Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). This variant has not been reported in the literature in individuals with ACADVL-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro270Glnfs*6) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. |