Table 3.
CKM missense variants detected in MTN-001 participants.
A total of 15 previously unreported CKM missense variants were detected in 15 heterozygous MTN-001 participants for the coding DNA reference sequence NM_001824.4. The functional consequence of resulting amino acid mutations were predicted using SIFT and PolyPhen in silico tools. A SIFT score < 0.05 was suggestive of a damaging amino acid substitution and > 0.05 a tolerated substitution. A PolyPhen score > 0.908 was suggestive of a probably damaging, 0.447–0.908 a possibly damaging, or < 0.447 a benign amino acid substitution. Deleterious and probably damaging CKM missense variants was observed at a frequency of 3% (4/142 individuals).
| Study site | Ethnicity | CKM variant (ref. > alt.) | cDNA position | Coding DNA sequence position | Protein position | Amino acid (ref. > alt.) | Exon | SIFT prediction | PolyPhen prediction |
|---|---|---|---|---|---|---|---|---|---|
| USA | European American | A > G | 419 | 244 | 82 | Y > H | 3/8 | Deleterious (0.02) | Possibly damaging (0.474) |
| USA | African American | T > C | 435 | 260 | 87 | E > G | 3/8 | Deleterious (0.04) | Possibly damaging (0.467) |
| SA | African | C > T | 462 | 287 | 96 | R > H | 3/8 | Tolerated (0.07) | Probably damaging (0.976) |
| UGA | African | G > A | 464 | 289 | 97 | H > Y | 3/8 | Deleterious (0) | Probably damaging (0.985) |
| UGA | African | C > T | 564 | 389 | 130 | R > H | 4/8 | Deleterious (0) | Probably damaging (0.966) |
| USA | European American | C > T | 674 | 499 | 167 | G > S | 5/8 | Deleterious (0.01) | Benign (0.307) |
| SA | African | A > G | 680 | 505 | 169 | F > L | 5/8 | Tolerated (1) | Benign (0.003) |
| USA | African American | A > G | 692 | 517 | 173 | Y > H | 5/8 | Deleterious (0) | Possibly Damaging (0.725) |
| USA | Hispanic | C > T | 758 | 583 | 195 | D > N | 5/8 | Tolerated (0.06) | Benign (0.099) |
| UGA | African | G > C | 779 | 604 | 202 | L > V | 5/8 | Deleterious (0.03) | Possibly damaging (0.878) |
| UGA | African | T > A | 969 | 794 | 265 | K > M | 7/8 | Deleterious (0) | Possibly damaging (0.799) |
| USA | African American | T > C | 981 | 806 | 269 | H > R | 7/8 | Tolerated (0.27) | Benign (0.002) |
| SA | African | A > T | 1080 | 905 | 302 | L > Q | 7/8 | Deleterious (0) | Probably damaging (0.919) |
| USA | African American | A > G | 1125 | 950 | 317 | L > P | 7/8 | Deleterious (0) | Probably damaging (0.999) |
| USA | European American | T > C | 1280 | 1105 | 369 | K > E | 8/8 | Tolerated (0.1) | Benign (0.001) |