Table 3.

Points per proband that can be applied toward PS2 and/or PS4 application based on proband phenotype and confirmed or assumed de novo status. Modified from “SVI Recommendation for De Novo Criteria (PS2 & PM6)” – Version 1.0

	Points per Proband
	PS2		PS4	Proband Phenotype (see Table 2)
Phenotypic Consistency	Confirmed	Assumed
Phenotype highly specific for gene	2	1	1	≥1 High OR ≥2 Moderate OR 1 Moderate AND ≥1 low OR High or moderate in 1st or 2nd-degree relative (unless known not to carry variant).†
Phenotype consistent with gene but not highly specific	1	0.5	0.5	IV. 1 Moderate
Phenotype consistent with gene but not highly specific and high genetic heterogeneity ‡	0.5	0.25	0	V. ≥1 Low

^†If PP1 is applied and the proband’s family contributed to the PP1 meiosis count, use IV (1 Moderate) instead of III.B to avoid double counting family history.

^‡Maximum allowable value of 1 may contribute to overall PS2 score to avoid counting multiple probands with only low-specificity phenotypes.