nsSNPs from dbSNP Predicted to Be Damaging Were Shown to Be Involved in Disease
| Melanocyte stimulating hormone receptor | ||
| Predictions supported by evidence | ||
| R151C | Damaging | Increased risk of cutaneous malignant melanoma (CMM) (Palmer et al. 1999). |
| R160W | Damaging | Doubles risk of CMM (Palmer et al. 1999). |
| D294H | Damaging | Doubles risk of CMM (Palmer et al. 1999). |
| L60V | Tolerated | No association with CMM (Palmer et al. 1999, Box et al. 2001). |
| R163Q | Tolerated | Detected from EST (Irizarry et al. 2000) and contig comparisons (Sachidanandam et al. 2001). No association with CMM (Box et al. 2001). |
| Prediction not supported by evidence | ||
| D84E | Damaging | Not associated with CMM (Healy et al. 1999; Palmer et al. 1999). |
| Peroxisome proliferator activated receptor α | ||
| Prediction supported by evidence | ||
| R127Q | Damaging | Detected in diabetic (Au et al. 1998; Brookes et al. 2000). |
| L162V | Damaging | Detected in diabetics and controls (Au et al. 1998; Brookes et al. 2000), but increases cholesterol and apolipoprotein B levels in diabetics, and perhaps nondiabetics (Flavell et al. 2000; Lacquemant et al. 2000; Vohl et al. 2000). |
| D304N | Damaging | Detected in diabetic (Au et al. 1998; Brookes et al. 2000). |
| R409T | Damaging | Detected in diabetic (Au et al. 1998; Brookes et al. 2000) |
| V227A | Tolerated | Found in similar frequencies in diabetics and nondiabetics (Au et al. 1998; Brookes et al. 2000; Hara et al. 2001). |
| A268V | Tolerated | Detected in diabetic (Au et al. 1998; Brookes et al. 2000) and EST comparison (Irizarry et al. 2000). No association with diabetes or coronary heart disease (Lacquemant et al. 2000). |
| Methylenetetrahydrofolate reductase (under balancing selection) | ||
| Prediction supported by evidence | ||
| A222V | Damaging | Common variant with diminished enzyme activity and increased risk of vascular disease and neural tube defects (Frosst et al. 1995) but also reduces risk of adult acute leukemia (Skibola et al. 1999), childhood leukemia (Wiemels et al. 2001), and colon cancer (Ma et al. 1997). |
| E429A | Damaging | Common variant with diminished enzyme activity (Weisberg et al. 1998) but reduces risk of adult acute leukemia (Skibola et al. 1999). |
| Effect unknown | ||
| R68Q | Damaging | Detected by comparison of contig to reference gene. |
| Fibrillin | ||
| Prediction supported by evidence | ||
| D1113G | Damaging | In Marfan patient (Liu et al. 1997/1998). |
| C1153Y | Damaging | In Marfan patient (Bairoch and Apweiler 2000). |
| I2023T | Damaging | In Marfan patient (Liu et al. 1997/1998). |
| C2038Y | Damaging | In Marfan patient (P. Oefner, pers. comm.) |
| C2053F | Damaging | In Marfan patient (P. Oefner, pers. comm.). |
| C2500S | Damaging | In Marfan patient (P. Oefner, pers. comm.). |
| G2514R | Damaging | In Marfan patient (P. Oefner, pers. comm.). |
| C2110R | Damaging | In Marfan patient (P. Oefner, pers. comm.). |
| C2170F | Damaging | In Marfan patient (P. Oefner, pers. comm.). |
| P1148A | Tolerated | In control individual (Liu et al. 1997/1998). |
| V2018I | Tolerated | In control individual (P. Oefner, pers. comm.). |
| Y2113F | Tolerated | In control individual (P. Oefner, pers. comm.). |
| D2329E | Tolerated | In control individual (P. Oefner, pers. comm.). |
| P2278S | Tolerated | In control individual (P. Oefner, pers. comm.). |
| Prediction not supported by evidence | ||
| S1077P | Tolerated | In Marfan patient (Liu et al. 1997/1998). |
| V1667I | Tolerated | In Marfan patient (Liu et al. 1997/1998). |
| N1341S | Tolerated | In Marfan patient (Liu et al. 1997/1998). |
| N1282S | Tolerated | In Marfan patient (Liu et al. 1997/1998). |
| Apolipoprotein A-I | ||
| Effect unknown | ||
| D126H | Damaging | Detected in individuals from either the top or bottom 2.5th percentile of a normalized blood pressure distribution (Halushka et al. 1999). |
| R184P | Damaging | Detected in individuals from either the top or bottom 2.5th percentile of a normalized blood pressure distribution (Halushka et al. 1999). |
| K131N | Tolerated | Detected from comparison of ESTs (Garg et al. 1999) and in an electrophoretic screening of newborns (von Eckardstein et al. 1990). |
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Five genes with a high fraction of nsSNPs from dbSNP predicted to be damaging; these nsSNPs have been shown to be involved in disease. The proteins that these genes code for are listed. Under each protein, the first column is the amino acid substitution caused by the nsSNP. For example, the first row under melanocyte stimulating hormone receptor gives the prediction for an nsSNP that corresponded to a change from the original amino acid R to amino acid C at position 151 in the melanocyte stimulating hormone receptor protein. The second column is the SIFT prediction for that particular amino acid substitution, and the third column is evidence supporting or conflicting with the prediction. Most predictions are supported by previously published evidence.
