Table 2 Correlation of the effect of substitution mutations on folding and observed disease phenotype. Mutations leading to severe phenotypes are highlighted in bold font. AS: Active site

1.

Human

H72L[25]

In AS

Disrupts AS

Lethal

(Type 3)

H200N [24], T355P [25],

P356R [25, 27],

E402K[25], S453Y[26]

Close to AS

Destabilizes the fold

Harmful

(Type 2)

W714R [25], R750W [25, 27],

G801D [28], L809P [25]

Away from AS

Minor

perturbation

Mild

or Viable

(Type 1)

2.

Bovine

R220H[21]

In AS

Disrupts AS

Lethal

(Type 3)

F320L[21]

Close to AS

Destabilizes the fold

Harmful

(Type 2)

3.

Guinea pig

R227W[29]

Close to AS

Destabilizes the fold

Harmful

(Type 2)