Submissions for variant NM_000018.4(ACADVL):c.797_798del (p.Pro266fs)

dbSNP: rs2071266269

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen	RCV001200801	SCV003853587	likely pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2023-01-10	reviewed by expert panel	curation	The NM_000018.4: c.797_798del (p.Pro266ArgfsTer31) variant in ACADVL is a frameshift variant predicted to 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). At least one individual with this variant was identified by newborn screen, but this information is insufficient to use toward classification (PMID: 26385305). 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 VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (ACADVL VCEP specifications version 1; approved November 8, 2021).
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV001200801	SCV001364966	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.797_798delCA (NP_000009.1:p.Pro266ArgfsTer31) [GRCH38: NC_000017.11:g.7222221_7222222del] 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	RCV001200801	SCV002160347	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2021-11-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 932845). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (PMID: 26385305). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro266Argfs*31) 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).