Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000801801 | SCV000941597 | uncertain significance | Deficiency of acetyl-CoA acetyltransferase | 2019-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 208 of the ACAT1 protein (p.Arg208Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in an individual with clinical features of beta-ketothiolase deficiency (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Arg208Gln and p.Arg208Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 17236799, Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |