ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 48 of the NR2E3 protein (p.Arg48Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive enhanced S-cone syndrome (PMID: 23374571; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1001884). 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 not expected to disrupt NR2E3 protein function with a negative predictive value of 80%. 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.