Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756948 | SCV000884942 | uncertain significance | not provided | 2018-03-11 | criteria provided, single submitter | clinical testing | The ACAD9 c.1798_1801delAAAG p.Lys600fs variant (rs917547961), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant introduces a frameshift in the final exon that is predicted to replace the 22 most C-terminal amino acids with a novel sequence of 56 amino acids. The functional consequences of such a change are not clear. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.001% (identified on 3 out of 277,168 chromosomes). Based on the available information, the clinical significance of the p.Lys600fs variant cannot be determined with certainty. |
| Fulgent Genetics, |
RCV001830653 | SCV002806984 | likely pathogenic | Acyl-CoA dehydrogenase 9 deficiency | 2024-03-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000756948 | SCV003291393 | pathogenic | not provided | 2024-05-06 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the ACAD9 gene (p.Lys600Cysfs*56). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 22 amino acid(s) of the ACAD9 protein and extend the protein by 33 additional amino acid residues. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ACAD9-related conditions. ClinVar contains an entry for this variant (Variation ID: 618501). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the ACAD9 protein in which other variant(s) (p.Pro616Ser) have been determined to be pathogenic (PMID: 25326637, 30831263). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001830653 | SCV004210054 | likely pathogenic | Acyl-CoA dehydrogenase 9 deficiency | 2024-02-19 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001830653 | SCV002081455 | uncertain significance | Acyl-CoA dehydrogenase 9 deficiency | 2020-11-05 | no assertion criteria provided | clinical testing |