Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521041 | SCV000619237 | likely pathogenic | not provided | 2017-07-25 | criteria provided, single submitter | clinical testing | The R325Q variant in the ACADS gene has been reported previously in the compound heterozygous state in a patient diagnosed with short-chain acyl-CoA dehydrogenase (SCAD) deficiency after an abnormal newborn screen (Huang et al., 2016). The R325Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R325Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R330C, R330H, E322K) have been reported in the Human Gene Mutation Database in association with SCAD deficiency (Stenson et al., 2014). A missense variant in the same residue (R325W) has also been reported, referred to as R301W, in an individual with increased ethylmalonic acid and undetectable short-chain acyl-CoA activity in fibroblasts, supporting a diagnosis of ethylmalonic aciduria/SCAD deficiency (Corydon et al., 2001). These variants further support the functional importance of this region of the protein. Therefore, we interpret R325Q as a likely pathogenic variant. |
| Counsyl | RCV000671262 | SCV000796219 | uncertain significance | Deficiency of butyryl-CoA dehydrogenase | 2017-12-07 | no assertion criteria provided | clinical testing | |
| Neonatal Disease Screening Center, |
RCV000671262 | SCV004800867 | likely pathogenic | Deficiency of butyryl-CoA dehydrogenase | no assertion criteria provided | clinical testing | PM2_P+PM3+PM5+PP3+PP4 |