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.