Total submissions: 5
| 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 | |
| Gene |
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, |
RCV000004029 | SCV001133031 | likely pathogenic | Deficiency of butyryl-CoA dehydrogenase | 2019-09-26 | no assertion criteria provided | clinical testing |