The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

In recognition of the urgent need for up-to-date variant classification resources, the ACMG and Association for Molecular Pathology released a landmark guidance document in 2015, 105 which has been implemented by US and international laboratories. Additional resources are outlined and include NCBI's ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/), which has quickly become a valuable centralized resource for clinically classified variants, and the Clinical Genome Resource (ClinGen, www.clinicalgenome.org), which serves as a centralized site for managing genomic knowledge surrounding genes and variants. With exome and genome sequencing being increasingly implemented, guidance has been issued by the ACMGG on how to deal with the incidental identification of variants in the so-called "actionable" genes in patients tested for unrelated conditions. 107 Additionally, quality assessment focusing on the informatics pipeline and variant interpretation could effectively utilize sequence data sets, as has been recently outlined. 108 The genetics and pathology communities are increasingly embracing data sharing, which will lead to needed improvements in divergent interpretation of gene sequence variants. These interpretative tasks would be beyond the scope of an FDA approval for a kit, or the CLIA oversight of an LDP, but have a critical impact on patient care based on genomic information.