Table 2.
Phenotype and Variant Details of Individuals With MC4R Mutations
| Phenotype details | ||||||||
| Amino acid change | p. G252D | p. F284I | p.R7S | p.M215I | p. V253I | p. F202L | p. I269N | p.F202L |
| c.DNA change | c.755 G>A | c.850 T>A | c.19C>T | c.645G>A | c.757 G>A | c.606 C>A | c.806 T>A | c.606 C>A |
| Center | BCH | BCH | BCH | BCH | CHOP | CHOP | CUMC | CUMC |
| Race or ethnicity | AA | Latino | AA | Latino | AA | AA | Latino | Latino |
| Sex | F | M | F | F | F | F | M | M |
| Birth weight, kg | 3.93 | 3.375 | ||||||
| Obesity class | 3 | 2 | 2 | 3 | 2 | 3 | 3 | 3 |
| First available age, mo | 48 | 24 | 28 | 37 | 36 | 81 | 0 | 0 |
| First available BMI, %BMI95pct | 153.1 | 119.5 | 119.7 | 133.3 | 165 | 124 | 90 | 50 |
| Last available age, mo | 203 | 87.7 | 87.5 | 160 | 99 | 123 | 80 | 33.5 |
| Last available height, cm | 169.5 | 125.2 | 133.5 | 167.3 | 154 | 145.5 | 119 | 92.7 |
| Last available height, percentile | 84.6 | 60.65 | 95.7 | 86.8 | >99 | 80 | 56 | 40 |
| Last available BMI, %BMI95pct | 152.3 | 126.6 | 140.3 | 200.6 | 132 | 174 | 130 | 148 |
| Last available BMI, kg/m2 | 45.01 | 24.23 | 27.94 | 56.9 | 34.87 | 33.4 | 22.3 | 26.3 |
| Age, mo | 215 | 99 | 87 | 160 | 98 | 123 | 71 | 33.5 |
| Height, cm | 169 | 130 | 134 | 167.3 | 152 | 145.5 | 116 | 92.7 |
| BP | ||||||||
| SBP, mm Hg (percentile) | 130 (94) | 99 (48) | 98 (40) | 127 (92) | 104 (53) | 129 (99) | 97 (59) | 95 (72) |
| DBP, mm Hg percentile) | 67 (50) | 50 (20) | 72 (86) | 65 (44) | 56 (24) | 60 (45) | 56 (65) | 49 (67) |
| Variant details | ||||||||
| gnomAD total allele frequency | 4.95E-05 | Absent | 4E-06 | 8E-06 | 6E-05 | 0.0009 | 0.00092 | 0.000898 |
| gnomAD allele frequency Africans | 0 | 0 | 0 | 0 | 0 | 0.00942 | 0 | 0.009415 |
| gnomAD allele frequency Latino | 0.00011 | 0 | 0 | 0 | 0.00011 | 0.00045 | 0.00731 | 0.000452 |
| Polyphen | Probably damaging | Probably damaging | Benign | Probably damaging | Probably damaging | Benign | Probably damaging | Benign |
| SIFT | Deleterious | Deleterious | Tolerated | Deleterious | Deleterious | Tolerated | Deleterious | Tolerated |
| CADD score | 28.6 | 26 | 12.25 | 28.7 | 25 | 12.17 | 26.8 | 12.17 |
| Functional | Novel | Novel | Novel | Known | Known | Known | Known | Known |
| References | Unpublished | Yeo, 2003; Farooqi, 2003; Nijenhuis, 2003; Lubrano-Berthelier, 2003 | Tao, 2005; Stutzmann, 2008; Hughes, 2009; Calton, 2009; Xiang, 2010; Hohenadel, 2014 | Tan, 2009; Calton, 2009; Thearle, 2012; Hohenadel, 2014; | Tao, 2005; Stutzmann, 2008; Hughes, 2009; Calton, 2009; Xiang, 2010; Hohenadel, 2014 |
Class 1 obesity, BMI 95%–120% of BMI95pct; class 2 obesity, BMI 120%–140% of BMI95pct; class 3 obesity, BMI >140% of BMI95pct. In silico prediction tools: CADD, Combined Annotation Dependent Depletion (https://cadd.gs.washington.edu/). A scaled CADD score of 20 means that a variant is among the top 1% of deleterious variants in the human genome. A scaled CADD score of 30 means that the variant is in the top 0.1%. Polyphen, Polymorphism Phenotyping (http://genetics.bwh.harvard.edu/pph2/); SIFT, Sorting Intolerant From Tolerant (https://sift.bii.a-star.edu.sg/) (5, 16–24).
Abbreviations: AA, African American; DBP, diastolic blood pressure; F, female; gnomAD, the Genome Aggregation Database (15); M, male; NA, not available; SBP, systolic blood pressure; TG, triglycerides.