Investigating the disease association of USH2A p.C759F variant by leveraging large retinitis pigmentosa cohort data.

Retinitis pigmentosa (RP) is an inherited retinal disease with a prevalence of 1/4,000. RP is highly genetically heterogeneous and there are over 80 genes associated with RP to date. One particular variant, p.C759F, has long been reported in RP cases but its pathogenicity was questioned by a recent study. Here, by leveraging large scale next-generation sequencing data from 982 non-Asian RP probands, we used binomial tests to evaluate the enrichment of this allele in RP cohort. We observed significant enrichment of this allele both in homozygous state and in compound heterozygous state with another protein-truncating allele. The results highlighted the clinical significance of the p.C759F allele in RP cases, which is important for accurate molecular diagnosis.