Description
This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 116 of the ACADM protein (p.Cys116Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 20434380). ClinVar contains an entry for this variant (Variation ID: 226076). 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 ACADM protein function with a positive predictive value of 80%. Studies have shown that this missense change is associated with inconclusive levels of altered splicing (PMID: 34923709). This variant disrupts the p.Cys116 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9158144, 19649258, 20567907, 29285339). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
