ClinVar

Description

The G703R variant has published previously in a patient who had an abnormal newborn screening result for long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency who also harbored the E510Q variant (Sykut-Cegielska et al. 2011). The G703R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (D701G) has been reported in the Human Gene Mutation Database in association with mitochondrial trifunctional protein (MTP) deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, the G703R variant was interpreted to be a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.