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. 2020 Sep 20;45(1):155–169. doi: 10.1038/s41366-020-00675-4

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].

(a)
CHR BP REF ALT Function Substitution SIFT Polyphen-2 MutationTaster PROVEAN ΔΔGa
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 Q115a . . 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 Hispanicb Penetrancec (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)
Q115b 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).