Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001352603 | SCV001547164 | uncertain significance | Deficiency of isobutyryl-CoA dehydrogenase | 2020-06-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glycine at codon 398 of the ACAD8 protein (p.Glu398Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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. 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 has not been reported in the literature in individuals with ACAD8-related conditions. This variant is not present in population databases (ExAC no frequency). |