ClinVar

Description

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.Arg227 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20574985, 26828774, Invitae and www.arup.utah.edu/database/OCTN2/OCTN2_welcome.php). 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 SLC22A5 protein function. This variant has not been reported in the literature in individuals with SLC22A5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 227 of the SLC22A5 protein (p.Arg227Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine.