Table 1. APE1 variants and predicted impact of amino acid change.

APE1 Variant	Source	% Frequency	Functional Consequence	SIFT	CupSat		PolyPhen
					Overall Stability	Torsion
Q51H	NCBI rs1048945	4.5	–	Possible AffectedFunction	Destabilizing	Unfavorable	Possible damaging
I64V	NCBI rs2307486	4.8	–	Tolerated	Destabilizing	Favorable	Resistant or no change
P112L	Tumor	Once	–	Tolerated	Destabilizing	Favorable	Resistant or no change
D148E	NCBI rs1130409	48.5	Normal AP endo*	Tolerated	Destabilizing	Favorable	Resistant or no change
R237C	Tumor	Once	–	Affected Function	Stabilizing	Unfavorable	Probably damaging
G241R	NCBI rs33956927	1.1	Normal (or increased) AP endo*	Tolerated	Stabilizing	Favorable	Resistant or no change
P311S	NCBI rs1803120	N/A	–	Affected Function	Stabilizing	Favorable	Probably damaging
A317V	NCBI rs1803118	N/A	–	Tolerated	Destabilizing	Unfavorable	Resistant or no change

Sorting intolerant from tolerant (SIFT) uses sequence homology to predict effects on protein function (http://sift.jcvi.org/). Scores <0.05 are considered deleterious, whereas those that are >0.5 are considered to be tolerated. The program polymorphic phenotypes (PolyPhen) predicts impact based on a set of empirical rules that apply to the protein’s sequence, phylogenetic and structural information (http://genetics.bwh.harvard.edu/pph/). Cologne University protein stability analysis tool (CupSat) predicts protein stability (http://cupsat.tu-bs.de/), and was employed using the PDB APE1 protein structure (1DE8).

^*Described previously in [33]. N/A = not available. Once = it was observed a single time.