Gene-Disease Relationships in Kidney Genetics

Genomic sequencing technologies are used in diagnostic laboratories to identify genetic causes of disease in patients. Gene curation plays an integral role by determining which genes have sufficient evidence for inclusion in diagnostic panels and those that should be prioritized in genome and exome sequencing. As the precursor to variant curation, gene curation also establishes pathogenicity limits for variant classification. Evaluating the clinical validity of a gene–disease relationship requires assessment of genetic and experimental evidence from literature and databases. The Clinical Genome Resource (ClinGen) has a semiquantitative framework for gene curation that is used across its Gene Curation Expert Panels (GCEPs). The ClinGen Kidney Disease Clinical Domain Working Group oversees five GCEPs covering the glomerulopathies, tubulopathies, complement-mediated kidney diseases, congenital anomalies of the kidney and urinary tract, and renal ciliopathies. These panels use a multidisciplinary approach in their gene curations, which are published and accessible to the public via the ClinGen website. ClinGen’s expert-informed curations and other resources outlined in this review will help nephrologists validate whether genetic findings in reports are clinically relevant to their patients. Empowering nephrologists with knowledge of gene curation principles is imperative for informed decision-making in patient care.