EZH2 Y646

CI-VAR-00004829Explore in graph →ClinVar 376218 CIViC 165

Curated evidence

Evidence by cancer (5 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–5 of 5 evidence items across 5 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Cutaneous Melanoma1
EZH2 Y646	GSK126	Predictive	D	Supports Sensitivity Response	2	accepted	EID1494 Preclinical study in melanoma cell lines. EZH2 expression was higher in EZH2 mutant (N=3) and wild-type melanoma cell lines (N=12) than untransformed cells (human epithelial melanocytes and human derm… (full text at CIViC) PMID 26304929 · Tiffen et al., 2015 · Open in CIViC	civic
Diffuse Large B-Cell Lymphoma1
EZH2 Y646	(diagnostic)	Diagnostic	B	Supports Positive	4	accepted	EID432 Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of GCB-DLBCL in 35 / 320 patient samples. In contrast, mutations in… (full text at CIViC) PMID 20081860 ·

ClinVar

Clinical significance (0)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

Data not yet available

No ClinVar interpretation attached to this variant.

Follicular Lymphoma1
EZH2 Y646	(diagnostic)	Diagnostic	B	Supports Positive	4	accepted	EID433 Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of Follicular non-Hodgkin Lymphoma in 18 / 251 patient samples. In … (full text at CIViC) PMID 20081860 · Morin et al., 2010 · Open in CIViC	civic

Melanoma1
EZH2 Y646	Dabrafenib + GSK126 + JQEZ5 + UNC1999Combination	Predictive	D	Supports Sensitivity Response	5	rejected	EID5677 Additional diseases: GC-DLBCL, Follicular lymphoma (FL). Y641 mutations are present in about 20% of GC-DLBCL, 10% FL, and 5% Melanoma (from TCGA/cBioportal). Also note that Y641 and Y646 mutations ar… (full text at CIViC) PMID 27135738 · Souroullas et al., 2016 · Open in CIViC	civic

Unmapped disease1unmapped disease
EZH2 Y646	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID9412 Using a baculovirus expression system, wild-type EZH2 or Y641 (Y641F, Y641H, Y641N, Y641S) mutants were coexpressed with the PRC2 complex in Spodoptera frugiperda cells. Methyltransferase activity ass… (full text at CIViC) PMID 21078963 · Sneeringer et al., 2010 · Open in CIViC	civic