Table 1

Prediction of effects of missense variants on protein function and stability

VariantFunction predictionStability prediction
SIFTMutation Taster2Mutation assessor§i-Mutant2.0MUpro††iStable‡‡
PredictionDDG valuePredictionConf. scorePredictionConf. score
c.3329G > A
DeleteriousDisease causingDecrease−1.02Decrease−0.68Decrease0.72
c.4027C > T
DeleteriousDisease causingMediumDecrease−1.23Decrease−1Decrease0.87

SIFT classifies an amino acid substitution as “deleterious” or “tolerated” according to the normalized probability. A substitution is predicted as deleterious if the score is < 0.05 and tolerated if the score is ≥ 0.05.

Mutation Taster2 predicts an alteration as one of 4 possible types: “disease causing,” “disease causing automatic”, “polymorphism,” and “polymorphism automatic.”

§Mutation assessor outputs the annotations of functional impact of a variant as functional (high, medium), predicted non-functional (low, neutral).

I-Mutant2.0 outputs free energy change value (DDG) between mutant and wild-type protein. Stability decreases if DDG < 0 and increases if DDG > 0.

††MUpro uses a confidence score between -1 and 1 to predict the effects of mutation on protein stability and measure the confidence of the prediction. A score < 0 means the mutation decreases the protein stability, and the smaller the score, the more confident the prediction. Conversely, a score > 0 means the mutation increases the protein stability, and the bigger the score, the more confident the prediction.

‡‡iStable outputs the prediction as “stability decrease” or “stability increase.”