Table 1.

Clinical, laboratory, and genetic features in patients with MC4R gene variants (+)

Case number	Sex/age (years)	Age at onset of obesity (years)	Height SDS/BMI SDS	Comorbidity	HOMA-IR	cDNA	Protein	ACMG/AMP	Mutation type	MT	SIFT	GERP	ExAC*#(overall allele frequency)	Novel
1	M/10	3	1.9/3.7	AN, IR	6.3	c.821 A > G/wt	p.N274S/wt	P	MS	DC	D	5.8499	0.00001647	–
2	F/8.6	2	1.9/2.7	IR, hepatosteatosis	4.4	c.496 G > A/wt	p.V166I/wt	UP	MS	DC	D	5.8499	0.00000879	–
3	M/8.5	2	3.2/4.6	IR, depression, social isolation	8.1	c.496 G > A/wt	p.V166I/wt	UP	MS	DC	D	5.8499	0.00000879	–
4	M/14	1	0.8/3.6	IR, hepatosteatosis, TSH elevation	7.3	c.407 C > T/wt	p.S136F/wt	UP	MS	DC	D	5.6999	–	–
5	M/2	0.6	1.8/7.3	IR	3.2	c.870delG/c.870delG	p.I291Sfs*10/ p.I291Sfs*10	LP	fs	DC	NA	6.0599	–	–
6	F/8	4	1.2/2.9	AN, IR	3.4	c.821 A > G/wt	p.N274S/wt	P	MS	DC	D	5.8499	0.0000176	–
7	F/14	2	1.0/3.1	IR, hepatosteatosis	4.6	c.407 C > T/wt	p.S136F/wt	US	MS	DC	D	5.6999	–	–
8	M/14.5	3	1.1/3.0	IR	6.2	c.821 A > G/wt	p.N274S/wt	P	MS	DC	D	5.8499	0.00001647	–
9	M/2.5	0.5	1.8/3.1	None	0.8	c.563C > T	p.S188L/wt	US	MS	DC	D	5.8499	0.00000879	+
10	M/13.3	3.5	− 1.4/3.2	IR, hepatosteatosis	4.6	c.493C > T	p.R165W/wt	US	MS	DC	D	5.8499	0.0000176	–
11	M/11.7	4	0.4/2.9	IR	3.7	c.597_599delCAT	p.M200del/wt	US	del	–	–	5.8499	–	+
12	M/16	5	2.8/3.8	IR/AN/hepatosteatosis/hypertension/TSH elevation	8.1	c.821A > G	p.N274S/wt	P	MS	DC	T	5.8499	0.0000176	–

*Exome Aggregation Consortium (http://exac.broadinstitude.org). ^# The allele frequency in the ExAC database does not contain representative controls for all ethnic groups

M male, F female, MS missense, NS nonsense, del deletion, fs frame shift, MT MutationTaster, DC disease causing, PD probably damaging, D damaging, T tolerated, NA not available, wt wild type, P pathogenic, LP likely pathogenic, US uncertain significance, SIFT sorting intolerant from tolerant, AN acanthosis nigricans, IR insulin resistance