Table 1.

Bioinformatic Assessment of 22 Missense Variants

Residue Change and Codon Position	Chromosome, Position (HG19)	MAF	Allele Change (Major to Minor)	rs Number	PolyPhen-2/SIFT
GCK
p.Ala11Thr	7, 44228522	0.0027	GCC-aCC	rs116093166	Probably damaging/tolerated
p.Thr396Sera	7, 44185162	0.0006	ACC-AgC	N/A	Benign/damaging
p.Glu272Alaa	7, 44187297	0.0003	GAG-GcG	N/A	Possibly damaging/tolerated
p.Val33Alaa,b	7, 44193010	0.0002	GTG-GcG	N/A	Possibly damaging/damaging
HNF4A
p.Thr139Ile	20, 43042364	0.0239	ACT-AtT	rs1800961	Benign/tolerated
NEUROD1
p.Thr45Alab	2, 182543455	0.3237	GCC-aCC	rs1801262	Benign/tolerated
p.Pro197Hisb	2, 182542998	0.0185	CCT-CaT	rs8192556	Possibly damaging/damaging
p.Val239Ileb	2, 182542873	0.0003	GTC-aTC	rs145050582	Benign/tolerated
p.Leu176Sera,b	2, 182543061	0.0002	TTA-TcA	N/A	Possibly damaging/damaging
p.His314Leua,b	2, 182542647	0.0006	CAC-CtC	N/A	Possibly damaging/damaging
HNF1A
p.Ser487Asnb	12, 121435427	0.2993	AGC-AaC	rs2464196	Benign/tolerated
p.Ala98Valb	12, 121416864	0.0239	GCC-GtC	rs1800574	Benign/tolerated
p.Gly574Serb	12, 121437382	0.0081	GGC-aGC	rs1169305	Benign/tolerated
p.Arg583Glnb	12, 121437410	0.0009	CGG-CaG	rs137853242	Benign/tolerated
p.Pro894Serb	12, 121432124	0.0003	CCA-tCA	rs151256267	Benign/tolerated
p.Ile27Leub	12, 121416650	0.2927	ATC-cTC	rs1169288	Benign/tolerated
p.Gly554Arg	12, 121437322	0.0005	GGG-aGG	N/A	Probably damaging/tolerated
HNF1B
p.Gly370Serb	17, 36070609	0.0009	GGC-aGC	rs113042313	Benign/tolerated
p.Asn228Lys	17, 33363607	0.0042	AAC-AAg	N/A	Benign/damaging
p.Ser547Phea,b	17, 36059095	0.0002	TCT-TtT	N/A	Probably damaging/damaging
p.Thr436Sera,b	17, 36064957	0.0002	ACA-tCA	N/A	Benign/tolerated
p.His332Glna	17, 36091635	0.0005	CAC-CAg	N/A	Probably damaging/tolerated

Major allele denoted by underline. We used the publicly available assessment tools PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2) and SIFT (http://sift.jcvi.org) to predict if amino acid changes could be detrimental to protein function (29–31). PolyPhen-2 predictions were based on the Hum Div testing model. This model was compiled from all damaging alleles with known effects on the molecular function causing human Mendelian diseases, present in the UniProtKB database, together with differences between human proteins and their closely related mammalian homologs, assumed to be nondamaging.

Abbreviation: N/A, not available.

^aIndicates a unique variant.

^bSNPs were consistent for both bioinformatics tools.