Gene sequencing panels are a powerful diagnostic tool for many clinical presentations
associated with genetic disorders. Advances in DNA sequencing technology have made
gene panels more economical, flexible, and efficient. Because the genes included on
gene panels vary widely between laboratories in gene content (e.g., number, reason
for inclusion, evidence level for gene-disease association) and technical completeness
(e.g., depth of coverage), standards that address technical and clinical aspects of
gene panels are needed. This document serves as a technical standard for laboratories
designing, offering, and reporting gene panel testing. Although these principles can
apply to multiple indications for genetic testing, the primary focus is on diagnostic
gene panels (as opposed to carrier screening or predictive testing) with emphasis
on technical considerations for the specific genes being tested. This technical standard
specifically addresses the impact of gene panel content on clinical sensitivity, specificity,
and validity-in the context of gene evidence for contribution to and strength of evidence
for gene-disease association-as well as technical considerations such as sequencing
limitations, presence of pseudogenes/gene families, mosaicism, transcript choice,
detection of copy-number variants, reporting, and disclosure of assay limitations.