ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.136C>T (p.Arg46Trp)

gnomAD frequency: 0.00008  dbSNP: rs121908003
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004029 SCV000220171 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2014-03-16 criteria provided, single submitter literature only
GeneDx RCV000185706 SCV000238627 likely pathogenic not provided 2022-06-10 criteria provided, single submitter clinical testing Published functional studies demonstrate increased protein degradation, reduced tetramer formation, increased aggregation tendency, and increased chaperone retention (Corydon et al., 1998; Pedersen et al., 2003); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14506246, 28516284, 18523805, 1692038, 22424739, 18676165, 28454995, 34426522, 31589614, 31980526, 33239584, 32778825, 9582344)
Invitae RCV000004029 SCV000940838 pathogenic Deficiency of butyryl-CoA dehydrogenase 2021-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 46 of the ACADS protein (p.Arg46Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121908003, ExAC 0.05%). This missense change has been observed in individuals with SCAD deficiency (PMID: 1692038, 18523805, 28454995). This variant is also known as R22W. ClinVar contains an entry for this variant (Variation ID: 3825). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt ACADS protein function. Experimental studies have shown that this missense change affects ACADS function (PMID: 9582344, 14506246). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004029 SCV000024195 pathogenic Deficiency of butyryl-CoA dehydrogenase 1989-11-01 no assertion criteria provided literature only
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000004029 SCV001133031 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2019-09-26 no assertion criteria provided clinical testing

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