SNP | Mutation | Damaging Effect | Conservation Score | Protein Stability (ΔΔG) |
---|
SIFT | phyloP | phastCons | GERP++ | I-Mutant3 | FoldX |
---|
rs2229094 | C13R | 0.783 (T) | 0.065 | 0.09 | 1.26 | −0.070 (N) | N/A |
rs2229092 | H51P | 0.253 (T) | 0.153 | 0.184 | −2.81 | 0.660 (I) | 1.180 (I) |
rs1041981 | T60N | 0.392 (T) | 0.073 | 0.936 | 3.15 | −0.520 (D) | −0.802 (D) |
- GEPR++, phyloP, and phastCons were applied to the LTα coding region to determine if common alleles at rs2229094, rs2229092 and rs1041981 are under evolutionary constraint across mammalian species. The SIFT algorithm was used to predict if a SNP has a (generally negative) effect on protein function. Variants with scores ranging from 0.05 to 1 were considered to be tolerated (T). We also predicted protein stability changes caused by missense mutations at these same three sites—as indicated by ΔΔG— using the FoldX [52] and I-Mutant3 [53] tools (I Increased, D Decreased, N Neutral; ΔΔG is in units of kcal/mol). The corresponding amino acid position, amino acid polymorphisms, and conservation scores are given for each SNP; N/A indicates that ΔΔG could not be calculated for rs2229094 using FoldX as outlined in the Methods section