ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.136C>T (p.Arg46Trp) (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 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing The R46W variant has previously been reported in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency (Naito et al., 1990). Functional analysis of R46W, reported as R22W, found that it is associated with increased degregation, reduced tetramer formation, increased aggregation tendency, and increased chaperone retention (Corydon et al., 1998; Pedersen et al., 2003). Therefore, we interpret R46W to be a pathogenic variant.
Invitae RCV000004029 SCV000940838 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2020-04-23 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 variant has been observed in combination with another ACADS variant in individuals affected with SCAD deficiency (PMID: 28454995, 18523805, 1692038). This variant is also known as R22W in the literature. ClinVar contains an entry for this variant (Variation ID: 3825). Experimental studies have shown that this missense change disrupts ACADS protein folding and abrogates enzymatic activity (PMID: 9582344, 14506246). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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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