Table 1 Residues selected for CRISPR introduction of single amino acid missense mutations

Naprt Variant	Variant class	Raw score	Rank overall^a	Rank at residue	Residue class	Residue rank*	SIFT scores
G497P	Impactful	−8.75	1 ↑	1 ↑	Sensitive	1 ↑	0.00
K532G	Impactful	−8.73	2 ↑	1 ↑	Sensitive	11 ↑	0.00
E147V	Impactful	−8.33	52 ↑	1 ↑	Sensitive	21 ↑	0.00
I618P	Neutral	−1.54	3,322 ↓	1 ↑	Tolerant	5 ↓	0.21
A262F	Neutral	−0.84	1,670 ↓	3 ↑	Tolerant	2 ↓	0.05

For each selected variant, we report its class (among impactful, mild and neutral), its raw predicted score and associated overall and relative ranks. In addition, we report the mutational sensitivity class (either tolerant or sensitive) and rank of the corresponding wild-type residue. For comparison, we indicate SIFT predicted normalised probabilities for the selected variants.
^*Residues with pLDDT < 70 are excluded from the ranking. This leaves us with 533 residues and 10,127 possible variants. The arrows indicate how the values are ordered to compute the ranks. For instance, a variant ranked 1 with an up arrow has the lowest (most negative) raw score. When some values are equal, they are assigned the same (minimum) rank. Sequencing validations of the five mutants are presented in Annex 1.

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