Heterozygous truncation variants in RCBTB1 have been reported to cause familial exudative vitreoretinopathy (FEVR). Such genotype-phenotype association is not supported by our recent study based on big data from our own, HGMD, and gnomAD. The authors, who reported association between RCBTB1 and FEVR, made further explanation on their own results without additional supporting data. In response to their comments, we would like to further clarify the pathogenesis of heterozygous truncation variants in RCBTB1 based on the current understanding of variant curation at individual gene level. Genes associated with FEVR are of great attention since it has been recognized as a common disease-causing blindness in children and adolescents. Curation of questionable causative genes or variant curation in well-known genes is a critical task in clinical gene test at the era of next-generation sequencing, since clinical application of biomarkers in questions may lead to inappropriate management or even disastrous consequence.
Keywords: RCBTB1; clinical application; familial exudative vitreoretinopathy; pathogenicity; truncation variants.