Table 2.

Summary of De Novo Single Nucleotide Variants (SNVs) in 343 SSC Families

SNV Effect	40× (High) Coverage		All Loci
	Proband	Sibling	Proband	Sibling	Proband F (29)	Proband M (314)	Sibling F (182)	Sibling M (161)	Both	Total
Splice site	4	1	6	3	1	5	1	2	0	9
Nonsense	15	7	19	9	3	16	6	3	2	30
Missense	125	121	207	207	19	188	116	91	3	417
Synonymous	53	42	79	69	8	71	43	26	4	152
Promoter	0	1	1	1	0	1	0	1	0	2
UTR	5	7	8	9	0	8	3	6	0	17
Intron	34	35	59	64	5	54	38	26	1	124
Intergenic	0	2	1	2	0	1	2	0	0	3
Total	236	216	380	364	36	344	209	155	10	754

De novo SNVs were tabulated according to affected status, gender, and type of mutation. Data under “40×coverage” indicate variants in the subset of the exome target region in which all members of a given family were covered by at least 40 sequence reads. The power to detect de novo variants in children from this well-covered portion of the target is very high, and we found no bias in coverage between affected and unaffected children. No significant difference was seen for missense mutations (125 in probands to 121 in unaffected siblings), but larger ratios of nonsense (15:7) and splice site (4:1) mutations were observed in probands relative to unaffected siblings. When we expanded our set of calls to include every variant that passed our thresholds (under “all loci”; see Experimental Procedures), similar ratios were observed. Probands and unaffected siblings are further subdivided based on gender: “proband F” indicates an affected female; “proband M” an affected male; “sibling F” an unaffected female; and “sibling M” an unaffected male. In parentheses, we indicate the number of children with the corresponding affected status and gender. The “both” column shows de novo SNVs that were shared by both siblings from the same family.