Table 1. Private variants shared by the affected cousins of each exome sequenced family. Genes selected for case-control study are noted in bold.
SIFT (Sorting Intolerant From Tolerant) predicts impact of amino acid substitutions based on the degree of conservation in sequence alignments derived from closely related sequences. Scores <0.05 are considered deleterious. PolyPhen-2 (Polymorphism Phenotyping v2) predicts impact of a variant on the structure and function of a human protein using eight sequence-based and three structure-based predictive features. Scores >0.95 are considered probably damaging. GERP (Genomic Evolutionary Rate Profiling) identifies functional constraint of a sequence variant by quantifying substitution deficits in multiple alignments. Substitution deficits represent a natural measure of constraint that reflects the strength of past purifying selection. Higher GERP scores are more deleterious.
| Family Id | Position | Gene | Nucleotide/ AA Change | SIFT | Polyphen2 | GERP |
|---|---|---|---|---|---|---|
| 74-0668 | chr14:104029378 | APOPT1 | c.C79A:p.P27T | 0.01 | 0 | −1.81 |
| chr19:35850022 | FFAR3 | c.A230G:p.N77S | 0.88 | 0.003 | −6.53 | |
| 152MM0304 | chr1:3328298 | PRDM16 | c.G1537A:p.G513S | 0.75 | 0.852 | 2.22 |
| chr2:167108286 | SCN9A | c.G3428T:p.C1143F | 0 | 1 | 5.82 | |
| 156-3860 | chr6:167594182 | TCP10L2 | c.A831T:p.E277D | 1 | 0 | −1.58 |
| chr8:144991583 | PLEC | c.G12364C:p.V4122L | 0.99 | 1 | 5.08 | |
| chr11:32636075 | CCDC73 | c.G1789C:p.E597Q | 0.41 | 0.047 | 1.63 | |
| chr19:55998317 | NAT14 | c.C615G:p.D205E | 0.1 | 0.009 | 0.636 | |
| 156-3897 | chr19:8399390 | KANK3 | c.C1321G:p.P441A | 0.23 | 0.131 | 3.36 |
| chr19:58117083 | ZNF530 | c.A190T:p.T64S | 0.79 | 0.001 | −3.39 | |
| 152MM0122 | chr2:233712266 | GIGYF2 | c.G3651C:p.Q1217H | 0.06 | 0.22 | −2.51 |