Establishment of the Clinical Genome Resource (ClinGen) X-Linked Inherited Retinal Disease Variant Curation Expert Panel

Inherited retinal diseases (IRDs) are a major cause of early onset blindness, profoundly affecting millions of patients. Given the clinical and genetic heterogeneity of IRD, targeted gene therapy is emerging as the main effective approach for treating the disease with many clinical trials currently underway. To maximize the benefit of these emerging therapies to patients, molecular diagnosis is the first critical step. In coordination with the Clinical Genome Resource (ClinGen) Ocular Clinical Domain Working Group (CDWG) committee, the ClinGen X-linked Inherited Retinal Disease Variant Curation Expert Panel (VCEP) was established to provide expert guidance on variant curation of seven X-linked IRD genes, including RPGR, CHM, RS1, RP2, OFD1, NDP, and CACNA1F. Curated variants of these X-linked IRD genes will be used as the standard for molecular diagnosis of patient variants. In this chapter, we describe the purpose of this ClinGen VCEP and outline strategies of establishing the curation rules.