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Patients referred to undergo family variant testing for a known pathogenic mutation were excluded.The gene panels analyzed for each patient were chosen at the discretion of the ordering provider and ranged from 2 to 79 genes.Clinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options.Many panels include lesser known breast cancer genes or genes associated with other cancers.The price of a panel was the same regardless of the number of genes, making test selection dependent only on patient and provider preferences.

In the absence of guidelines for choosing appropriately from the increasing variety of panels, oncology providers must determine whether to select high-risk panels limited to genes with established medical management guidelines or larger panels that have dozens of genes associated with a variety of non-breast hereditary cancers.

The frequency of P/LP variants in genes with established management guidelines was compared and evaluated for consistency with personal and family histories.

This study identified 1131 P/LP variants and compared variants in clinically actionable genes for breast and non-breast cancers.

In groups B and C, a significant percentage of P/LP variants (28.5 and 31.8%, respectively) were identified in genes associated with increased risk of non-breast cancers for which established management guidelines exist (see Appendix 1 in Electronic Supplementary Material).

Perhaps surprisingly, 132 P/LP variants (11.7%) were unexpected clinically actionable findings (i.e., variants in genes for which patients had no suggestive personal or familial history and for which medical management guidelines exist).

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