Table 1.

Classification of variants according to ENIGMA [16]

Class	Description	Probability of being Pathogenic		Clinical implication [16]
		According to IARC [9]	According to ACMG/AMP [19]
1	Benign (B)/ of no clinical significance	< 0.001	< 0.001	Treat as if ‘no mutation detected’ for this disorder No Predictive testing of at risk relatives is suggested
2	Likely benign (LB)/ of little clinical significance	0.001–0.049	0.001–0.099
3	Variant of unknown significance (VUS)	0.050–0.949	0.100–0.899	Surveillance based on family history and patient-based risk factors Obtaining additional data in order to reclassify, if possible Research testing of family members can be recommended
4	Likely pathogenic (LP)	0.950–0.999	0.900–0.999	Full high-risk surveillance Predictive testing of at-risk relatives is suggested
5	Pathogenic (P)	> 0.999	> 0.999

In our study, we do not distinguish between pathogenic and likely pathogenic outcomes, but refer to them as P/LP