Summary of functional assays for phenotypic ERG variants in this study
Variant . | Phenotypes . | Transactivation . | DNA binding . | Subcellular localization . | FLC myeloid differentiation . | FLC cytokine independence . | Leukemogenesis assay . | ACMG classification . |
---|---|---|---|---|---|---|---|---|
WT | NA | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | NA |
I126T | AML | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
P116R | Cytopenia | ✓✓✓✓ | ✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | VUS |
R302C | CLL | ✓✓✓✓ | ND | ✓✓✓✓ | ND | ND | ND | VUS |
K380N | Cytopenia | ✓✓✓✓ | ✓✓✓ | ✓ | ND | ND | ND | P |
P306L | Lymphedema | ✓✓✓ | ND | ✓✓✓✓ | ND | ND | ND | VUS |
G394W | AML | ✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
M341V | Cytopenia | ✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
D345N | MDS | ✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✖ | VUS |
D363A | MDS | ✓✓ | ✖ | ✓✓✓✓ | ND | ND | ND | VUS |
Y388C | Lymphedema | ✖ | ND | ✓✓✓✓ | ND | ND | ND | LP |
R370H | Cytopenia | ✖ | ✖ | ✓✓ | ND | ND | ND | P |
R370P | Cytopenia + MDS | ✖ | ✖ | ✓✓ | ✖ | ✖ | ✖ | P |
Y373C | Cytopenia + AML | ✖ | ✖ | ✓ | ✖ | ✖ | ✖ | LP |
Y372∗ | Cytopenia | ✖ | ✖ | ✓ | ✖ | ✖ | ✖ | P |
E20Vfs∗13 | MDS | ND | ND | ND | ND | ND | ND | VUS |
V127Efs∗82 | ALL | ND | ND | ND | ND | ND | ND | VUS |
Variant . | Phenotypes . | Transactivation . | DNA binding . | Subcellular localization . | FLC myeloid differentiation . | FLC cytokine independence . | Leukemogenesis assay . | ACMG classification . |
---|---|---|---|---|---|---|---|---|
WT | NA | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | NA |
I126T | AML | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
P116R | Cytopenia | ✓✓✓✓ | ✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | VUS |
R302C | CLL | ✓✓✓✓ | ND | ✓✓✓✓ | ND | ND | ND | VUS |
K380N | Cytopenia | ✓✓✓✓ | ✓✓✓ | ✓ | ND | ND | ND | P |
P306L | Lymphedema | ✓✓✓ | ND | ✓✓✓✓ | ND | ND | ND | VUS |
G394W | AML | ✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
M341V | Cytopenia | ✓✓ | ✓✓✓✓ | ✓✓✓✓ | ND | ND | ND | VUS |
D345N | MDS | ✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✓✓✓✓ | ✖ | VUS |
D363A | MDS | ✓✓ | ✖ | ✓✓✓✓ | ND | ND | ND | VUS |
Y388C | Lymphedema | ✖ | ND | ✓✓✓✓ | ND | ND | ND | LP |
R370H | Cytopenia | ✖ | ✖ | ✓✓ | ND | ND | ND | P |
R370P | Cytopenia + MDS | ✖ | ✖ | ✓✓ | ✖ | ✖ | ✖ | P |
Y373C | Cytopenia + AML | ✖ | ✖ | ✓ | ✖ | ✖ | ✖ | LP |
Y372∗ | Cytopenia | ✖ | ✖ | ✓ | ✖ | ✖ | ✖ | P |
E20Vfs∗13 | MDS | ND | ND | ND | ND | ND | ND | VUS |
V127Efs∗82 | ALL | ND | ND | ND | ND | ND | ND | VUS |
ERG variants are ordered in descending order of transactivation ability. Ticks (✓) indicate degree of WT-like activity in transactivation, DNA binding, subcellular localization, FLC myeloid differentiation, FLC cytokine independence, and leukemogenesis assays. ✖ indicates complete LOF in these assays.
CLL, chronic lymphocytic leukemia; LP, likely pathogenic; NA, not applicable; ND, not determined; P, pathogenic.