Table 4.

Heterogeneity analysis by bioinformatic groups

	Previous estimatesa			This study: P+VLP+VUS			This study: VLP+VUS
Bioinformatic group	NVAR	Estimate	95% CI	NVAR	Estimate	95% CI	NVAR	Estimate	95% CI
Missense variants	1177	0.12	0.08–0.17	2032	0.13	0.10–0.17	2007	0.09	0.06–0.13
Not in key domain	854	0.0	0.0–0.04	1507	0.019	0.0–0.05	1506	0.008	0.0–0.05
In key domain	323	0.35	0.26–0.45	525	0.44	0.35–0.53	501	0.36	0.26–0.44
C0	242	0.01	0.0–0.06	277	0.23	0.11–0.35	277	0.23	0.11–0.35
C15–C25	58	0.29	0.09–0.56	73	0.42	0.17–0.68	72	0.40	0.15–0.65
C35–C55	55	0.66	0.34–0.93	48	0.51	0.23–0.79	43	0.38	0.07–0.69
C65	98	0.81	0.61–0.95	127	0.76	0.59–0.92	109	0.59	0.28–0.90
Potential splice variants
High damage to wild type	94	0.97	0.82–1.00	108	0.91	0.77–1.0	67	0.77	0.52–1.0
Moderate damage to wild type	66	0.34	0.15–0.55	49	0.79	0.54–1.0	40	0.61	0.27–0.95
Increased de novo donor	8	0.64	0.06–0.98	26	0.14	0.0–0.43	25	0.0	0.0–0.32
Moderate de novo donor	7	0.30	0.0–0.88	48	0.15	0.0–0.40	48	0.15	0.0–0.40
All de novo donor	15	NA	NA	74	0.14	0.0–0.33	73	0.08	0.0–0.26

CI confidence interval, NVAR number of variants, P pathogenic variant, VLP likely pathogenic variant, VUS variant of unknown significance.

^aEaston et al.,² Tavtigian et al.,³ Vallee et al.⁵