ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1389dup (p.Thr464fs)

dbSNP: rs398123082
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV002286566 SCV002576777 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2022-08-23 reviewed by expert panel curation The c.1389dup (p.Thr464AspfsTer3) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 14/20 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). To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. To our knowledge, functional assays have not been reported for this variant. 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_Supporting (ClinGen ACADVL VCEP specifications version#1; 08-04-2022).
Eurofins Ntd Llc (ga) RCV000174651 SCV000225984 pathogenic not provided 2012-10-05 criteria provided, single submitter clinical testing
Invitae RCV002286566 SCV003271953 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2021-12-26 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: 92275). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr464Aspfs*3) 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).
Baylor Genetics RCV002286566 SCV004214007 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-10-31 criteria provided, single submitter clinical testing

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