Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497466 | SCV000589305 | likely pathogenic | not provided | 2016-04-13 | criteria provided, single submitter | clinical testing | The c.989_990delGCinsAT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.989_990delGCinsAT variant is not observed in large population cohorts (Lek et al., 2016). The c.989_990delGCinsAT variant causes the replacement of the normal Arginine at codon 330 with a Histidine, denoted p.Arg330His (R330H). The R330H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. A R330H missense change caused by a different nucleotide change (c.989 G>A) and a different missense change at codon 330 (R330C) have both been reported in patients with SCAD deficiency (van Maldegem et al. 2006). An R330H missense change caused by a different nucleotide change (c.989 G>A) and a different missense change at codon 330 (R330C) have both been reported in patients with SCAD deficiency (van Maldegem et al. 2006). In summary, the c.989_990delGCinsAT variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Labcorp Genetics |
RCV000984238 | SCV002108227 | pathogenic | Deficiency of butyryl-CoA dehydrogenase | 2023-08-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg330 amino acid residue in ACADS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16926354, 18676165; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 431801). A different variant (c.989G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 16926354, 26274329; Invitae). This suggests that this variant is also likely to be causative of disease. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 330 of the ACADS protein (p.Arg330His). |
| Counsyl | RCV000984238 | SCV001132322 | uncertain significance | Deficiency of butyryl-CoA dehydrogenase | 2018-03-23 | no assertion criteria provided | clinical testing |