Table 3.

Description and consequences of each variant pathogenicity classification in the five-category system.

Label	Consequence
Pathogenic (P)	A healthcare provider can use molecular testing information in clinical decision-making, for breeding programs and/or screening.
Likely pathogenic (LP)	A health-care provider can use the molecular testing information in clinical decision-making when combined with other evidence of the disease in question, for breeding programs and/or screening.
Variant of uncertain significance (VUS)	Not to be used in clinical decision-making, for breeding programs or screening. Efforts to resolve the classification of the variant as pathogenic or benign should be undertaken.
Likely benign (LB)	A healthcare provider can conclude that it is not the cause of the patient’s disorder when combined with other information. It should not be used for breeding programs and/or screening.
Benign (B)	A healthcare provider can conclude that it is not the cause of the patient’s disorder. It should not be used for breeding programs and/or screening.

Each category is linked to specific recommendations in terms of clinical decision making, inclusion in breeding and screening programs. Between P and LP, mainly the strength of the evidence varies, while the practical differences are limited. Similarly, the practical differences between VUS, LB, B also have limited consequences. The most significant health and breeding decisions would occur when a variant switches between the pathogenic (P/LP) and the benign/uncertain classifications (VUS/LB/B), which can happen when new information becomes available or when label assignment differs between evaluators, hence the importance of a high inter-evaluator agreement on classification.