ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1269+1del

dbSNP: rs2071340733
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV001247120 SCV002769775 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2022-12-14 reviewed by expert panel curation The c.1269+1del variant in ACADVL occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 12. It is predicted to cause skipping of biologically-relevant-exon 12/20, resulting in an in-frame deletion (removes amino acids 395-423) that is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate). To our knowledge, this variant has not been reported in an individual affected with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. To our knowledge, no functional studies have been performed on this variant. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1_Moderate, PM2_Supporting (VCEP specifications version1; approved November 8, 2021)
Labcorp Genetics (formerly Invitae), Labcorp RCV001247120 SCV001420525 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-14 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu424Argfs*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.

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