Table1.

Categories of gene panels

Panel category	Examples of genes	Penetrance	Quality of management guidelines	Cancer and associated health risks	VUS rate	Implications for relatives
Site/organ system-specific panel-e.g. breast cancer
High-penetrance genes only	BRCA1, BRCA2, APC, PTEN, TP53, MLH1, MSH2, MSH, PMS2, STK11, CDH1, MUTYH	High	Strong evidence-based clinical actionable guidelines for management of cancer and related health risks	Risk profiles well-defined	Low 2%-10%	Quantifiable risk and risk management profile
High and moderate penetrance genes-clinically actionable	The genes above plus ATM, CHEK2, PALB2	Moderate	Moderate evidence for increased surveillance at certain cancer sites	Risk profiles defined for some cancers, but the full spectrum of risks undetermined	Moderate 10%-20%	Incomplete risk and management profile
Low penetrance/newly described genes	The genes above plus RAD50, RAD51C, RAD51D, BRIP1, BARD1 POLE, POLD1	Low or unknown	Lack of evidence-based guidelines. Management based on personal and family history and literature review	Suspected but uncertain cancer risks	High>20%	Poorly defined
Multiple organ systems panel
Pan-cancer panel	Various combinations of high-, moderate-, and low- penetrance genes	Unknown to high	Varied evidence or case-based management depending on gene mutation identified	Varied potential for identifying a mutation in a highly or moderately penetrant gene that does not currently fit the known medical history	High>20%	Depends on the gene