ClinVar Miner

Submissions for variant NM_000018.3(ACADVL):c.1748C>G (p.Ser583Trp) (rs1085307648)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000675075 SCV000800571 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2017-07-28 criteria provided, single submitter clinical testing
GeneDx RCV000489971 SCV000576934 likely pathogenic not provided 2018-12-27 criteria provided, single submitter clinical testing The S583W missense variant was previously identified in a 3-month-old with hypoketotichypoglycemia, hypotonia, hepatomegaly, elevated long chain acylcarnitine levels, and dicarboxylicaciduria in whom a second variant in ACADVL was not identified (Souri et al., 1998). The S583Wvariant has also been reported in individuals with positive newborn screens for very long chainacyl-CoA dehydrogenase (VLCAD) deficiency, although it is unknown if these individuals harboredanother ACADVL gene variant (Miller et al., 2015). Functional analyses found that S583W isassociated with impaired dimerization and 19% residual enzyme activity compared to wild type (Souriet al., 1998). The S583W variant is not observed in large population cohorts (Lek et al., 2016; 1000Genomes Consortium et al., 2015; Exome Variant Server). The S583W variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position that is conservedacross species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. In summary, this variant is likely pathogenic; however, the possibility that it isbenign cannot be excluded.

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