Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pediatrics, |
RCV000844768 | SCV000966034 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000844768 | SCV001372352 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2020-06-08 | criteria provided, single submitter | clinical testing | Variant summary: ACAT1 c.83_84delAT (p.Tyr28CysfsX38) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 241332 control chromosomes (gnomAD). c.83_84delAT has been reported in the literature in multiple individuals (both compound heterozygous and homozygous) affected with Mitochondrial Acetoacetyl-CoA Thiolase Deficiency (Fukao_1997, Su_2017, Paquay_2017). These data indicate that the variant is very likely to be associated with disease. Fibroblasts obtained from a compound heterozygous individual carrying the variant of interest and another pathogenic variant showed very low levels of RNA and protein (Fukao_1997). Enzymatic activity measured in fibroblasts from homozygous individuals also showed reduced enzymatic activity (Paquay_2017). One ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000844768 | SCV002237112 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr28Cysfs*38) 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 (rs749873354, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 9090533). ClinVar contains an entry for this variant (Variation ID: 666463). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000844768 | SCV004212850 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-08-19 | criteria provided, single submitter | clinical testing |