ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1748C>T (p.Ser583Leu) (rs1085307648)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665031 SCV000789086 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-01-06 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000665031 SCV001364941 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1748C>T (NP_000009.1:p.Ser583Leu) [GRCH38: NC_000017.11:g.7224711C>T] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 15210884. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000665031 SCV001472293 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-09-19 criteria provided, single submitter clinical testing The ACADVL c.1748C>T; p.Ser583Leu variant (rs1085307648) is reported in the literature in multiple individuals affected with very long chain acyl-coA dehydrogenase (VLCAD) deficiency, some of whom had significantly lower VLCAD enzyme activity (Bujan 2014, Campbell 2005, Miller 2015, Ohashi 2004). This variant is reported in ClinVar (Variation ID: 550315), and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The serine at codon 583 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at this codon (c.1748C>G; p.Ser583Trp) has been reported in individuals with VLCAD deficiency (Miller 2015). Based on available information, this variant is considered to be pathogenic. References: Bujan N et al. Characterization of CoQ10 biosynthesis in fibroblasts of patients with primary and secondary CoQ10 deficiency. J Inherit Metab Dis. 2014 Jan;37(1):53-62. Campbell CD et al. Two newborns with nutritional vitamin B12 deficiency: challenges in newborn screening for vitamin B12 deficiency. Haematologica. 2005 Dec;90(12 Suppl):ECR45. Miller MJ et al. Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Mol Genet Metab. 2015 Nov;116(3):139-45. Ohashi Y et al. A new diagnostic test for VLCAD deficiency using immunohistochemistry. Neurology. 2004 Jun 22;62(12):2209-13.

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