ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1276G>A (p.Ala426Thr)

dbSNP: rs1419478766
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817166 SCV000957712 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 426 of the ACADVL protein (p.Ala426Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of very long chain acyl-CoA dehydrogenase deficiency (PMID: 30950014, 34704412). ClinVar contains an entry for this variant (Variation ID: 660045). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADVL protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ACADVL function (PMID: 33150772). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000817166 SCV001365095 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1276G>A (NP_000009.1:p.Ala426Thr) [GRCH38: NC_000017.11:g.7223819G>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PM1, PP3
Baylor Genetics RCV000817166 SCV004210900 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-09-19 criteria provided, single submitter clinical testing

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