ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1198G>A (p.Val400Met)

gnomAD frequency: 0.00001  dbSNP: rs149116708
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666127 SCV000790371 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2017-03-16 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000666127 SCV001365086 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1198G>A (NP_000009.1:p.Val400Met) [GRCH38: NC_000017.11:g.7223659G>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: PP4, BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV000666127 SCV002174119 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 400 of the ACADVL protein (p.Val400Met). This variant is present in population databases (rs149116708, gnomAD 0.0009%). This missense change has been observed in individual(s) with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PMID: 26385305, 27538624). ClinVar contains an entry for this variant (Variation ID: 551143). 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%. 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.
Fulgent Genetics, Fulgent Genetics RCV000666127 SCV002783453 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666127 SCV004215092 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-03-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004754523 SCV005359426 likely pathogenic ACADVL-related disorder 2024-06-26 no assertion criteria provided clinical testing The ACADVL c.1198G>A variant is predicted to result in the amino acid substitution p.Val400Met. This variant has been reported with another ACADVL variant in individuals with clinical and/or biochemical features consistent with very long chain acyl-CoA dehydrogenase deficiency (VLCADD, Yamamoto et al. 2016. PubMed ID: 27538624; Vallejo et al. 2021. PubMed ID: 34194748). In one individual, Western blot analysis of their fibroblast cells demonstrated reduced VLCAD protein expression and a skin biopsy confirmed the diagnosis (Yamamoto et al. 2016. PubMed ID: 27538624). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic.

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