2.1| Gene disease validity assessment and gene characterization
Our diagnostic laboratory has established standardized guidelines for curating and scoring GDV which have been independently validated (Smith, 2017). Briefly, the tiered system is similar to the ClinGen model and scores evidence of gene-disease relationships as definitive, strong, moderate, limited, no reported evidence, and conflicting evidence reported (Strande, 2017). A team of scientists reviews published peer-reviewed literature on an ongoing basis and determines the GDV score for each gene-disease relationship. Scores of “moderate” or higher are considered characterized, and those with a score of “limited” or lower are uncharacterized. Some genes have evidence to support associations with more than one phenotype, inheritance pattern or disease mechanism. This could include genes with multiple characterized associations or more a combination of characterized and uncharacterized associations. Gene-disease relationships classified as “limited” by GDV assessment may be included as an uncharacterized candidate for clinical reporting purposes. Genes with supporting evidence, but that do not meet reporting criteria are not included on reports but may be reported as ‘notable’ findings and are available to clinicians by way of filtered variant lists (Farwell Hagman, 2017).