ClinVar

Description

Variant summary: ACADVL c.1054A>G (p.Met352Val) results in a conservative amino acid change located in the Acyl-CoA dehydrogenase/oxidase, C-terminal domain (IPR009075) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250952 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1054A>G has been reported in the literature in an unknown or presumed compound heterozygous state in at least 2 individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (example, Andresen_1999, Huang_2022), including in at least 1 individual undergoing newborn screening. These report(s) do not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 9973285, 35193651). ClinVar contains an entry for this variant (Variation ID: 2851878). Based on the evidence outlined above, the variant was classified as uncertain significance.