Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001058332 | SCV001222892 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2022-11-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ACAT1 protein in which other variant(s) (p.Gly418Asp) have been observed in individuals with ACAT1-related conditions (PMID: 28689740). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 853510). This frameshift has been observed in individual(s) with clinical features of beta-ketothiolase deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the ACAT1 gene (p.Gln404Hisfs*66). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the ACAT1 protein and extend the protein by 41 additional amino acid residues. |