ClinVar Miner

Submissions for variant NM_000017.2(ACADS):c.815G>A (p.Arg272His) (rs374726386)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664591 SCV000788580 uncertain significance Deficiency of butyryl-CoA dehydrogenase 2017-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000185688 SCV000238609 likely pathogenic not provided 2017-04-11 criteria provided, single submitter clinical testing The R272H variant waspreviously reported in a homozygous state in an individual with significant ethylmalonic aciduria andsignificantly elevated butyrylcarnitine in plasma (van Maldegem et al., 2006). This individual was alsohomozygous for the common G209S variant in the ACADS gene (van Maldegem et al., 2006). TheR272H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016;1000 Genomes Consortium et al., 2015; Exome Variant Server). The R272H variant is a conservativeamino acid substitution, which is not likely to impact secondary protein structure as these residuesshare similar properties. This substitution occurs at a position that is conserved across species. In silicoanalysis predicts this variant is probably damaging to the protein structure/function. Another missensevariant in the same residue (R272C) has been reported in the Human Gene Mutation Database inassociation with SCAD deficiency (Stenson et al., 2014), supporting the functional importance of thisregion of the protein. In summary, the R272H variant is likely pathogenic; however, the possibilitythat it is benign cannot be excluded.

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