ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1062CAT[1] (p.Ile356del)

dbSNP: rs754325237
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671665 SCV000796660 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2017-12-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000671665 SCV000820525 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2025-01-11 criteria provided, single submitter clinical testing This variant, c.1065_1067del, results in the deletion of 1 amino acid(s) of the ACADVL protein (p.Ile356del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754325237, gnomAD 0.09%). This variant has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 28871440; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 555781). For these reasons, this variant has been classified as Pathogenic.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000671665 SCV001365205 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1065_1067delCAT (NP_000009.1:p.Ile356del) [GRCH38: NC_000017.11:g.7222853_7222855del] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant dose not meet any evidence codes reported in the ACMG guidelines.
GeneDx RCV001540648 SCV001758553 uncertain significance not provided 2019-06-19 criteria provided, single submitter clinical testing In-frame deletion of one amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28871440)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001779050 SCV002014970 uncertain significance not specified 2021-10-19 criteria provided, single submitter clinical testing Variant summary: ACADVL c.1065_1067delCAT (p.Ile356del) results in an in-frame deletion that is predicted to remove isoleucine amino acid from the encoded protein. The variant allele was found at a frequency of 4.4e-05 in 250762 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in ACADVL causing Very Long Chain Acyl-CoA Dehydrogenase Deficiency (4.4e-05 vs 0.0029), allowing no conclusion about variant significance. c.1065_1067delCAT has been reported in the literature in compound heterozygous individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (Gillingham_2017, Elizondo_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000671665 SCV002049384 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2021-11-25 criteria provided, single submitter clinical testing The ACADVL c.1065_1067delCAT; p.Ile356del variant (rs754325237) is reported in the literature in multiple individuals affected with VLCAD deficiency (Gillingham 2017). This variant is reported in ClinVar (Variation ID: 555781) and is found in the Ashkenazi Jewish population with an allele frequency of 0.1% (10/10366 alleles) in the Genome Aggregation Database. This variant deletes a single isoleucine residue leaving the rest of the protein in-frame. However, given the lack of clinical and functional data, the significance of the p.Ile356del variant is uncertain at this time. References: Gillingham MB et al. Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial. J Inherit Metab Dis. 2017 Nov;40(6):831-843.PMID: 28871440.
Baylor Genetics RCV000671665 SCV004212648 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-02-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000671665 SCV005650592 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2024-04-02 criteria provided, single submitter clinical testing

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