ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg239 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been observed in individuals with RDH12-related conditions (PMID: 16269441, 24474277), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RDH12 protein function. ClinVar contains an entry for this variant (Variation ID: 536988). This missense change has been observed in individual(s) with autosomal recessive inherited retinal dystrophy and/or Leber congenital amaurosis (PMID: 31456290, 32141364, 35006499; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 239 of the RDH12 protein (p.Arg239Leu).