Table 1.
Spectrum of TET1, TET3 and ASXL2 mutations and variants of unclear significance in patients with MDS/MPN overlap syndromes
| Gene | Chr | Position | Nucleotide nomenclature | Protein consequence | Disease type | Alt Frac | ExAC | dbSNP | Cosmic # | Cited as somatic | Cosmic Annotated Disease Type | Exon | Phenotype Prediction | Concurrent Mutations |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TET1 | 10 | 70404533 | c.2047C > G | Q683E | CMMLb | 46% | 0.08400% | rs139785845 | COSM327333 | yes | ALL1, Sezary Syndrome2 | 4 | MODERATE | TET3Y473a (43%) ASXL1G646Wfsa12 (26%) PTPN11N308D (14%) |
| 70450700 | c.5540G > T | G1847V | MDS/MPNu | 52% | n/a | n/a | n/a | 12 | MODERATE | SRSF2P95R (53%) NRASG13D (41%) | ||||
| TET3 | 2 | 74274463 | c.1419C > A | Y473 a | CMMLb | 43% | n/a | n/a | n/a | 3 | HIGH | TET1Q683E (46%) ASXL1G646Wfsa12 (26%) PTPN11N308D (14%) | ||
| 74329187 | c.5278_5280del | K1760del | CMML | 48% | 0.02900% | rs564392898 | n/a | 11 | MODERATE | PHF6F172Lfsa46 (88%) | ||||
| 74327798 | c.3883G > A | V1295I | CMML | 51% | 0.04400% | rs199849765 | n/a | 11 | MODERATE | CEBPAH195_P196dup (57%) ATML1111P (51%) ASXL1L775a (49%) JARID2R767K (46%) | ||||
| 74327893 | c.3980_3981insACTGAG | N1326_S1327insRL | CMMLa | 41% | 0.00860% | rs768310475 | n/a | 11 | MODERATE | SRSF2P95T (45%) TET3L1328P (42%) | ||||
| 74327898 | c.3983T > C | L1328P | CMMLa | 42% | 0.00860% | rs767538752 | n/a | 11 | MODERATE | SRSF2P95T (45%) TET3N1326_S1327insRL (41%) | ||||
| 74328177 | c.4262C > G | P1421R | CMML | 51% | 0.00940% | rs745953793 | n/a | 11 | MODERATE | SH2B3R140H (58%) JARID2P1229L (52%) NRASQ61K (47%) RUNX1G199W (21%) | ||||
| 74329152 | c.5237G > T | W1746L | MDS/MPNu | 49% | 0.06500% | rs190925009 | n/a | 11 | MODERATE | SRSF2P95L (49%) ASXL1P808H (49%) JAK2V617F (49%) | ||||
| ASXL2 | 2 | 25966302 | c.2902_2903dupCT | P969Cfs a 10 | MDS/MPNu | 22% | n/a | . | n/a | 13 | HIGH | SRSF2P95_R102del (15%) RUNX1R237K (38%) | ||
| 25967305 | c.1901C > A_p.Ser634X | S634 a | MDS/MPNu | 20% | n/a | . | n/a | 13 | HIGH | SRSF2R94dup (39%) | ||||
| 25965934 | c.3272 C>T_p.Ala1091Val | A1091V | CMML | 51% | 0.01300% | rs781151810 | n/a | 13 | MODERATE | ZRSR2 c.400-2A > G (92%) MPLV368L (49%) ASXL1G646Wfsa12 (44%) SETBP1D868N (43%) RUNX1T246Hfsa15 (35%) | ||||
| 26101079 | c.13G > A_p.Gly5Arg | G5R | MDS/MPNu | 51% | 0.01200% | rs371056638 | n/a | 1 | MODERATE | EZH2 c.1411-1G > A (91%) ASXL1R417a (45%) JARID2R326C (48%) SUZ12N263H (47%) |