P688: Impact of gene-disease specific guidelines on variant reclassification in a clinical hereditary cancer setting

Germline findings in hereditary cancer genetic testing can help inform clinical management decisions regarding screening, surgery, and treatment interventions. The 2015 American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) guidelines have streamlined the variant curation process, however, interpretation of variants of uncertain significance (VUS) remains challenging. Gene-disease specific modifications to the 2015 ACMG/AMP guidelines have been released by ClinGen Variant Curation Expert Panels (VCEPs), which may help resolve difficulties relating to VUS interpretation, including reclassification to a meaningful category (Likely pathogenic/pathogenic (LP/P) or likely benign/benign (LB/B).