International Journal of Obesity

Table 2 (a) Annotation of newly identified variants in MC4R coding region. (b) Number of individuals harboring the new MC4R variants per race/ethnicity and estimated penetrance for obesity (BMI ≥ 30) and overweight (BMI ≥ 25) [23].

From: Evaluation of the MC4R gene across eMERGE network identifies many unreported obesity-associated variants

(a)
CHR	BP	REF	ALT	Function	Substitution	SIFT	Polyphen-2	MutationTaster	PROVEAN	ΔΔG^a
18	58038610	G	T	Nonsynonymous	L325I	T	B	N	N	−1.12
18	58038660	T	A	Nonsynonymous	E308V	D	D	D	D	−1.2
18	58038661	C	T	Nonsynonymous	E308K	D	D	D	D	−1.76
18	58038666	C	T	Nonsynonymous	S306N	D	D	D	N	−1.36
18	58038684	A	G	Nonsynonymous	L300P	D	D	D	D	−3.2
18	58038691	C	T	Nonsynonymous	D298N	D	D	D	D	−0.68
18	58038708	CATG	C	Inframe deletion	I291del	.	.	.	.
18	58038768	G	C	Nonsynonymous	P272R	D	D	D	D	−1.85
18	58038774	G	A	Nonsynonymous	S270F	D	D	D	N	−0.79
18	58038802	A	G	Nonsynonymous	F261L	D	P	D	D	−0.86
18	58038805	G	C	Nonsynonymous	P260A	D	D	D	D	−1.74
18	58038841	T	C	Nonsynonymous	T248A	D	P	D	D	0.26
18	58038856	C	G	Nonsynonymous	G243R	D	D	D	D	0.02
18	58038876	C	T	Nonsynonymous	R236H	T	B	D	N	−1.89
18	58038885	C	A	Nonsynonymous	G233V	T	B	D	N	−0.43
18	58038898	G	A	Nonsynonymous	L229F	T	P	D	D	−1.37
18	58038999	A	G	Nonsynonymous	I195T	D	D	D	D	−1.57
18	58039072	T	C	Nonsynonymous	S171G	T	B	D	N	−1.4
18	58039078	T	C	Nonsynonymous	I169V	T	B	D	N	−1.47
18	58039155	A	C	Nonsynonymous	I143S	D	D	D	D	−2.5
18	58039209	A	T	Nonsynonymous	I125N	D	D	D	D	−1.65
18	58039240	G	A	Stop-gain	Q115^a	.	.	D	.
18	58039242	G	A	Nonsynonymous	A114V	T	B	N	N	−0.3
18	58039251	T	A	Nonsynonymous	D111V	T	B	D	N	0.67
18	58039281	G	C	Nonsynonymous	T101S	D	D	D	D	−0.12
18	58039344	T	A	Nonsynonymous	Y80F	D	D	D	D	−1.9
18	58039353	G	A	Nonsynonymous	S77L	D	D	D	D	−1.55
18	58039377	A	T	Nonsynonymous	I69K	D	D	D	D	−3.45
18	58039431	A	C	Nonsynonymous	F51C	D	P	D	D	−0.93
18	58039435	C	A	Nonsynonymous	V50L	T	D	D	N	−0.78
18	58039580	C	T	Start-loss	M1I	D	B	N	N	−1.07
18	58039582	T	C	Start-loss	M1V	D	B	N	N	−0.78

(b)
Substitution	N carriers	EA	AA	Asian	Other	Unknown	Hispanic^b	Penetrance^c (BMI ≥ 30)	Penetrance (BMI ≥ 25)
L325I	2	1	.	.	.	1	1	1 (2/2)	1 (2/2)
E308V	2	1	1	.	.	.	.	0.65 (1/2)	0.65 (1/2)
E308K	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
S306N	1	1	.	.	.	.	.	0	1 (1/1)
L300P	1	.	1	.	.	.	.	0	0
D298N	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
I291del	1	1						0	1 (1/1)
P272R	1	1	.	.	.	.	1	1 (1/1)	1 (1/1)
S270F	2	2	.	.	.	.	.	1 (2/2)	1 (2/2)
F261L	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
P260A	1	.	1	.	.	.	.	0	0
T248A	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
G243R	1	.	.	.	.	.	.	0	1 (1/1)
R236H	2	2	.	.	.	.	.	1 (1/1), 1 missing BMI	1 (1/1), 1 missing BMI
G233V	1	.	.	.	.	.	.	1 (1/1)	1 (1/1)
L229F	1	1	.	.	.	.	.	0	0
I195T	1	.	.	1	.	.	.	0	0
S171G	1	.	.	1	.	.	.	0	1 (1/1)
I169V	1	.	.	1	.	.	.	0	0
I143S	1	1	.	.	.	.	.	0	1 (1/1)
I125N	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
Q115^b	1	.	.	1	.	.	.	0	1 (1/1)
A114V	1	1	.	.	.	.	.	0	1 (1/1)
D111V	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
T101S	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
Y80F	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
S77L	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
I69K	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
F51C	1	1	.	.	.	.	.	1 (1/1)	1 (1/1)
V50L	1	1	.	.	.	.	.	0	1 (1/1)
M1I	1	.	1	.	.	.	.	0	0
M1V	1	.	1	.	.	.	.	0	1 (1/1)

More detail annotations are included in Supplementary Table S2.
SIFT (D deleterious (sift ≤ 0.05), T tolerated (sift > 0.05)); PolyPhen (D probably damaging (≥0.957), P possibly damaging (0.453–0.956), B benign (≤0.452)); MutationTaster (D disease causing; N polymorphism, probably harmless); PROVEAN (D deleterious, N neutral), ΔΔG unfolding free energy difference between the wild type and mutant protein [25, 29], EA European Americans, AA African Americans.
^aUnfolding free energy difference between the wild type and mutant protein (ΔΔG).
^bRace (EA-AA-Asian-Other-Unknown) and ethnicity (Hispanic and non-Hispanic) annotated separately.
^cThe penetrance estimate using population allele frequency (see “Methods”), (x/y = number of carriers with outcome vs total carriers).

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