Table 2

Variants identified in additional genes

Patient no.	Gene	DNA change	Protein effect	PolyPhen-2	SIFT	Class	gnomAD allele frequency	Molecular function	RNA expression in human β-cells (RPKM)^*
43	CASP10	c.104del	p.Asp35Valfs^*10	—	—	4	—	Protease	0.2
44	DACH1	c.454_456dup	p.Ser152dup	—	—	4	—	DNA binding	6.9
45	GCKR	c.1484T>G	p.Val495Gly	0.96	0	4	—	Carbohydrate binding	0.1
6^†	HGFAC	c.711C>G	p.Cys237Trp	1	0	4	0.00026	Protease	0
46	HGFAC	c.711C>G	p.Cys237Trp	1	0	4	0.00026	Protease	0
18^†	KCNQ1	c.498C>A	p.Phe166Leu	0.967	0.05	4	—	Potassium channel	0.3
47	MC4R	c.230C>T	p.Ser77Leu	0.855	0	4	—	G-protein–coupled receptor	0
48	RFX2	c.1894G>A	p.Ala632Thr	0.999	0	4	—	DNA binding	3.9
49	RREB1	c.3218C>T	p.Ser1073Leu	0.988	0.02	4	—	DNA binding	9
50	SLC5A1	c.932A>T	p.Lys311Met	0.999	0	4	—	Glucose:sodium symporter	3.5
51	SLC5A1	c.1415T>C	p.Leu472Pro	0.892	0	4	—	Glucose:sodium symporter	3.5
52	SLC5A1	c.1415T>C	p.Leu472Pro	0.892	0	4	—	Glucose:sodium symporter	3.5
53	TMPRSS6	c.2263A>G	p.Lys755Glu	0.998	0.01	4	—	Peptidase	4.4
54	ZBED3	c.211C>G	p.Leu71Val	0.977	0	4	—	DNA binding	8.3

Summary of all class 4 (likely pathogenic) variants identified in genes not yet associated with MD. Classification of the variants according to the methodology of Richards et al. (12). PolyPhen-2 score considered pathogenic if >0.47 and SIFT <0.05. gnomAD, Genome Aggregation Database; RPKM, reads per kilobase per million mapped reads.
* Nica et al. (13).
†The variants in the HGFAC and KCNQ1 genes are not likely to be causative for diabetes because the two identified carriers also had a GCK variant and a classical GCK diabetes phenotype. The HGFAC variant may also be considered to be too frequent in the gnomAD database to be an MD variant (26).