ClinVar

Description

This sequence change replaces arginine with proline at codon 296 of the CPT2 protein (p.Arg296Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with CPT2 deficiency (Invitae database). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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. 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. Other missense substitutions at this codon (p.Arg296Gln and p.Arg296Leu) have been reported in individuals affected with CPT2 deficiency (PMID: 14615409, 21913903).