Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001378913 | SCV001576607 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2020-10-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ACADM-related conditions. 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. This variant disrupts the p.Ile78 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24623196, 22630369). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 78 of the ACADM protein (p.Ile78Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |