Table 6.

Results from the three different analysis programs used to predict the pathogenicity of novel missense changes

	SIFT	PolyPhen	PMUT
p.G44R	Affect (Score 0.01)	Probably damaging	Pathogenic (NN output 0.5113)
p.N2377S	Tolerated (Score 0.44)	Possibly damaging	Neutral (NN output 0.2372)
p.N2394K	Tolerated (Score 0.23)	Possibly damaging	Neutral (NN output 0.5113)
p.G3546R	Affect (Score 0.01)	Probably damaging	Pathogenic (NN output 0.1799)
p.N3894D	Tolerated (Score 0.05)	Probably damaging	Neutral (NN output 0.0522)
p.E4921K	Tolerated (Score 0.85)	Benign	Neutral (NN output 0.3130)

SIFT: SIFT Score ranges from 0 to 1. The amino acid substitution is predicted to be damaging if the score is < 0.05, and tolerated if the score is 0/> 0.05.

PolyPhen: "Probably damaging" (it is believed most likely to affect protein function or structure), "Possibly damaging" (it is believed to affect protein function or structure), "Benign" (most likely lacking any phenotypic effect).

PMUT: NN output is the original output from the neural network for this mutation and its parameters. If that output is bigger than 0.5 it is predicted as pathogenic, otherwise as neutral.