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Table 2 Predictions of amino acid changes on LTα protein function

From: Multiple selective sweeps of ancient polymorphisms in and around LTα located in the MHC class III region on chromosome 6

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)

  1. 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