EZH2 Y646C

CI-VAR-00004830Explore in graph →NP_004447.2:p.Tyr646CysNM_004456.5:c.1937A>GCIViC 3607

Curated evidence

Evidence by cancer (6 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 1–6 of 6 evidence items across 4 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
B-Cell Non-Hodgkin Lymphoma1
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G	Tazemetostat	Predictive	A	Supports Sensitivity Response	2	accepted	EID11220 In a multicentre, open-label, phase 1 trial, tazemetostat was evaluated in 64 adult patients (≥18 years) with relapsed or refractory B-cell non-Hodgkin lymphoma (n=21) or advanced solid tumours (n=43)… (full text at CIViC) PMID 29650362 · Italiano et al., 2018 · Open in CIViC	civic
Diffuse Large B-Cell Lymphoma1
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G	Tazemetostat	Predictive	B	Supports Sensitivity Response	3	accepted	EID11110 This phase II study evaluated the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese adults with relapsed or refractory B-cell non-Hodgkin lymphoma harboring EZH2-activating mutations …

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 Lymphoma2
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G	(oncogenic)	Oncogenic	B	Supports Oncogenicity	4	accepted	EID11111 In this large cohort study, 366 patients with follicular lymphoma (FL) were recruited to investigate the incidence and distribution of EZH2 mutations. NGS and Sanger detected EZH2 positive mutations i… (full text at CIViC) PMID 24052547 · Bödör et al., 2013 · Open in CIViC	civic
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G	Tazemetostat	Predictive	B	Supports Sensitivity Response	4	accepted	EID11109 In this study, Koji Izutsu et al. conducted a multicenter, open-label phase II clinical trial to evaluate the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese patients with relapsed … (full text at CIViC) PMID 34159682 · Izutsu et al., 2021 · Open in CIViC	civic

Unmapped disease2unmapped disease
EZH2 Y646C	(functional)	Functional	D	Supports Loss Of Function	2	accepted	EID9868 EZH2 mutations were identified in a screen of 614 patients with myeloid malignancies. Several mutations in the highly conserved CXC-SET domains were expressed in Sf9 insect cells along with polycomb r… (full text at CIViC) PMID 20601953 · Ernst et al., 2010 · Open in CIViC	civic
EZH2 Y646C	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID11052 Authors of this study identified and detailed the role of USP47, a novel deubiquitinase (DUB), that stabilizes mutated EZH2 in cancers and prevents the protein’s degradation by ubiquitination. Degrada… (full text at CIViC) PMID 35034955 · Yang et al., 2022 · Open in CIViC	civic