Table 1.

Characteristics of the Three Candidate Variants Identified in Affected Members of Family 616

	Genes
SEC23B	C16orf72	PTPN2
Genomic positiona	chr20: 18,529,290	chr16: 9,186,804	chr18: 12,794,321
DNA variant	c.1781T>G	c.253T>C	c.1204G>A
Protein alteration	p.Val594Gly	p.Ser85Pro	p.Ala402Thr
Predicted Effect of Missense Variants
Condelb	deleterious	deleterious	deleterious
MutationTaster	disease causing	disease causing	polymorphism
MutPred g score (>0.5)	0.785	0.525	0.578
CADD scorec	22.2	23.2	9.28
Evolutionary Conservation and Allele Frequency
PhyloPd	4.572	2.882	1.282
PhastConse	1	1	0.994
NHLBI ESPf MAF	G = 0, T = 13,006	C = 0, T = 12,994	T = 0, C = 13,006
Tissue-Specific Protein Levelsg
Thyroid	+	−	+
Breast	+	−	+
Endometrium	+	−	+

^aGenomic positions correspond to the UCSC hg19 reference assembly.

^bCondel combines multiple prediction software algorithms (SIFT, PolyPhen-2, and MutationAssessor).

^cCADD-scaled C score ≥ 20 indicates variants within the top 1% of likely deleterious variants across the human genome.

^dPhyloP scores range between −14 and +6; conserved sites have positive scores.

^ePhastCons scores range between 0 and 1; values closer to 1 have a higher probability of nucleotide conservation.

^fNHLBI Exome Sequencing Project (ESP) Exome Variant Server (see Web Resources) v.0.0.28 (accessed May 9, 2015).

^gData analyzed from the Human Protein Atlas for immunohistochemically stained normal and cancer tissues.