2.6 | Data Analysis
To assess the overall impact of our laboratory’s involvement with GeneMatcher, we analyzed the outcomes of our submissions to date. For purposes of this analysis, duplicate entries for a candidate gene-disease relationship with the same inheritance, zygosity, and alteration type were consolidated and counted as a single entry. We retrospectively reviewed all our DES cases from 2011 through January 2021 and tabulated the number of probands with reported alterations in genes with a GeneMatcher entry. For genes with more than one disease association, we only counted cases associated with the phenotype related to the GeneMatcher entry. We assessed the classification of the gene at the time of the initial report (uncharacterized, characterized, or notable), the current GDV score (uncharacterized, moderate, strong, or definitive) and the number of probands who received a reclassification report due to gene characterization. Fisher exact test was used for statistical analysis.
To quantify our laboratory’s contribution to disease gene discovery efforts, we queried PubMed (https://pubmed.ncbi.nlm.nih.gov/) for peer-reviewed publications focused on gene characterization efforts which listed authors affiliated with Ambry Genetics. These articles were reviewed for content and categorized as (1) description of new gene-disease association, (2) follow-up case report or supportive evidence (i.e., functional or animal model evidence), (3) follow-up descriptive cohort, and (4) follow-up expansion of phenotype. Publications which included a broadening and further defining of the phenotypic spectrum but not a major expansion in the phenotype were counted as a follow-up descriptive cohort. We cross referenced this published gene list with our GeneMatcher submissions.