Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Shenzhen Institute of Pediatrics, |
RCV000239383 | SCV000297740 | likely pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2015-03-07 | criteria provided, single submitter | clinical testing | |
Department of Pediatrics, |
RCV000239383 | SCV000966073 | likely pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | literature only | |
Invitae | RCV000239383 | SCV003440314 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2022-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 218 of the ACAT1 protein (p.Ser218Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 27264805). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 252925). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACAT1 protein function. For these reasons, this variant has been classified as Pathogenic. |