Table 3 Novel missense variants predictions.

From: A novel deep intronic variant strongly associates with Alkaptonuria

Predicted protein change

mCSM-stability

Distance to interface

mCSM-PPI2

Distance to ligand

mCSM-Lig

Category of missense variant*

HGDiscovery Prediction

p.(Thr196Ile)

Destabilizing (−0.48 kcal/mol)

23.2 Å

Decreased affinity (−0.41 kcal/mol)

24.8 Å

Decreased affinity (−1.94 log)

Protomer destabilization

Pathogenic

p.(Gly362Arg)

Destabilizing (−0.17 kcal/mol)

14.9 Å

Decreased affinity (−0.59 kcal/mol)

10.3 Å

Decreased affinity (−1.27 log)

Protomer destabilization, hexamer disruption, and active site disruption

Pathogenic

  1. *The classes are not necessarily mutually exclusive. The largest effect of both variants is on the stability of the protomer; but Gly362Arg is also likely to disrupt the formation of the hexamer and ligand binding.
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