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These three missense mutations were predicted to be damaging in functional prediction by SIFT and PolyPhen2.

Antigenic-index alterations following L1 mutations were predicted by Jameson Wolf algorithm.

The majority of the mutations are predicted to cause an up-regulation of the pathway; hence they are gain-of-function mutations.

More mutations are predicted than in the core, seemingly in order to optimise the network of complementary interactions between polar and charged groups.

We find that qualitative effects of individual mutations are predicted quite well (Fig. S4).

In an additional challenge, steady state gene levels in response to double knockout mutations were predicted.

Both mutations are predicted to confer amino acid changes but their impact on gene function is unknown.

In the HGMD dataset, more missense mutations were predicted to be deleterious by the SVMpolynomial combination than nsSNPs from dbSNP.

SNAP predicted only 1731 (11.3%) of these mutants to be neutral, so the great majority of mutations were predicted to be non-neutral.

Nearly all of these indel mutations are predicted to create frameshift mutations although a few frame-preserved mutations are also observed.

In the HGMD dataset, the majority of missense mutations were predicted to be deleterious by SIFT (65.2%) and PANTHER (70.6%), and to be damaging by Polyphen (73.6%).