Submissions for variant NM_000018.4(ACADVL):c.128del (p.Gly43fs)

dbSNP: rs2071123075

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen	RCV001063280	SCV002538684	likely pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2022-04-06	reviewed by expert panel	curation	The c.128del (p.Gly43Valfs*18) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20 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 2.1.1 (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant. To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. In summary, this variant has been classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Curation Expert Panel: PVS1, PM2_Supporting (ACADVL VCEP specifications v2.0; Approved on 11/10/2021).
Invitae	RCV001063280	SCV001228118	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2023-09-05	criteria provided, single submitter	clinical testing	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: 857574). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly43Valfs*18) 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).