Table 4.

Individually significant genes identified from the analysis of de novo mutations from patients with intellectual disability. Genes with multiple functional de novo mutations across 151 cases of intellectual disability (ID)^9,10. Loss-of-function (LoF) mutations include nonsense, frameshift, and splice site-disrupting mutations. The genome-wide significance threshold is 1×10⁻⁶. The number of mutations is either compared to the expected number for LoF only or for both LoF and missense, as indicated by the “# DNMs Expected” and “Test” columns.

Gene	Mutations	#LoF	#Missense	# DNMs Expected	p-value	Test
SYNGAP1	splice/frameshift/frameshift	3	0	0.0017	8.15E-10	LoF
SCN2A	missense/nonsense/frameshift/frameshift	3	1	0.0025	2.56E-09	LoF
SCN2A	missense/nonsense/frameshift/frameshift	3	1	0.0187	5.01E-09	LoF+mis
STXBP1	missense/missense/splice	1	2	0.0071	5.87E-08	LoF+mis
TCF4	missense/missense	0	2	0.0069	2.39E-05	LoF+mis
GRIN2A	missense/missense	0	2	0.0162	1.34E-04	LoF+mis
TRIO	missense/missense	0	2	0.0333	5.60E-04	LoF+mis