Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000627576 | SCV000748576 | pathogenic | not provided | 2018-04-18 | criteria provided, single submitter | clinical testing | The c.1033_1034delGA variant in the ACAT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1033_1034delGA variant causes a frameshift starting with codon Glutamic acid 345, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Glu345ArgfsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1033_1034delGA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1033_1034delGA as a pathogenic variant. |
Department of Pediatrics, |
RCV000844832 | SCV000966110 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research | |
Invitae | RCV000844832 | SCV002130322 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-07-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu345Argfs*9) in the ACAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACAT1 are known to be pathogenic (PMID: 7749408). This variant is present in population databases (rs781496140, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with beta-ketothiolase deficiency (aka mitochondrial acetoacetyl-CoA thiolase deficiency) (PMID: 28255778). ClinVar contains an entry for this variant (Variation ID: 524080). |
Baylor Genetics | RCV000844832 | SCV004210542 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-09-09 | criteria provided, single submitter | clinical testing |