Table 1.

Summary of clinical, biochemical, and genetic data of the six patients who turned out as positive at NGS for a variant of uncertain significance (VUS), likely pathogenic or pathogenic. All the variants were inherited in heterozygosity.

Patient	Gender	Age at the Hyperglycemia	BG (mg/dL) HbA1c at First Observation	Phenotype	Therapy	Family History	Gene	Nucleotide Change	Amino Acid	Segregation	Allele Frequency (gnomAD)	PolyPhen-2 SIFT	ClinVar Classification	Literature Reports
1	M	18	110–170 6–6.5%	-	None	Mother and grandmother on OHA	WFS1	c.124C > T	p.Arg42Ter	Mother	0.00009	Pathogenic	Pathogenic/Likely pathogenic	[15]
2	M	10	300 >9%	Congenital cataract	Insulin 0.8 IU/kg/day	Mother with mild/moderate hyperglycemia	WFS1	c.1153G > A	p.Glu385Lys	Mother	0.00057	VUS	VUS/Likely benign	[16]
3	F	12	>400 16.8%	-	Metformin	Father with DM on insulin and metformin; sister on insulin	WFS1 BLK	c.1249T > G c.211G > A	p.Arg42Ter p.Ala71Thr	Father, sister Father	0.01485	VUS benign	VUS Benign/Likely benign	[17]
4	M		400 8.9%	-	Sulfonylurea	Father with DM on insulin	KCNJ11	c.685G > A	p.Glu229Lys	Father	-	Likely pathogenic	Pathogenic/Likely risk allele	[18]
5	M	15	436 9.1%	-	Insulin	Brother and sister with diabetes; three sisters on OHA; mother with T2D	INS	c.187 + 2T > C	Intron variant	Mother, 2 brothers, and 4 sisters	-	Pathogenic	Pathogenic	[19]
6	M	13	491 8.6%	Normal abdomen US	Insulin 0.66 IU/kg/day	Father and grandmother with T2D	HNF1B	c.704G > A	p.Arg235Gln	Father and grandmother	-	Pathogenic	Likely pathogenic/VUS	[20]

BG: blood glucose, HbA1c: glycated hemoglobin, T2D: type 2 diabetes, OHA: oral hypoglycemic agent.