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).