Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001037931 | SCV001201368 | uncertain significance | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2019-03-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ACADM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with serine at codon 185 of the ACADM protein (p.Ile185Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. 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. This variant disrupts the p.Ile185 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20434380, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |