Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001753708 | SCV001985819 | pathogenic | not provided | 2021-10-27 | criteria provided, single submitter | clinical testing | Functional analysis of R433Q found it is associated with significantly reduced ACAD9 activity compared to wild-type (Schiff et al., 2015); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25721401, 30025539, 26669660, 28284481) |
| Labcorp Genetics |
RCV001753708 | SCV003525354 | uncertain significance | not provided | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 433 of the ACAD9 protein (p.Arg433Gln). This variant is present in population databases (rs781156571, gnomAD 0.0009%). This missense change has been observed in individual(s) with mitochondrial complex I deficiency (PMID: 25721401). ClinVar contains an entry for this variant (Variation ID: 242462). 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 ACAD9 protein function. Experimental studies have shown that this missense change affects ACAD9 function (PMID: 25721401). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401190 | SCV004121812 | uncertain significance | not specified | 2023-10-18 | criteria provided, single submitter | clinical testing | Variant summary: ACAD9 c.1298G>A (p.Arg433Gln) results in a conservative amino acid change located in the Acyl-CoA dehydrogenase/oxidase, C-terminal (IPR009075) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251412 control chromosomes (gnomAD). c.1298G>A has been reported in the literature in an individual affected with Mitochondrial Complex I Deficiency (Schiff_2015, Collet_2016). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity. The following publications have been ascertained in the context of this evaluation (PMID: 25721401, 26669660). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV003469176 | SCV004209460 | likely pathogenic | Acyl-CoA dehydrogenase 9 deficiency | 2024-02-28 | criteria provided, single submitter | clinical testing |