Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Pediatrics, |
RCV000844823 | SCV000966100 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV000844823 | SCV001233383 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2024-02-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 317 of the ACAT1 protein (p.Asp317Asn). This variant is present in population databases (rs780486838, gnomAD 0.005%). This missense change has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 27748876, 28689740, 29624230). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 666515). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACAT1 protein function. Experimental studies have shown that this missense change affects ACAT1 function (PMID: 27748876). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000844823 | SCV004210442 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-11-08 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000844823 | SCV005681160 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2024-04-22 | criteria provided, single submitter | clinical testing |