EZH2 Y646N

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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 Lymphoma5
EZH2 Y646N	(oncogenic)	Oncogenic	D	Supports Oncogenicity	4	accepted	EID11013 A selective EZH2 inhibitor (EI1) was used to target the EZH2 Y641N mutation in DLBCL cell lines. EI1 treatment significantly inhibited proliferation in EZH2-mutated cells compared to lymphoma cells wi…

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

Supports Sensitivity Response

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 Lymphoma5

EZH2 Y646N

(oncogenic)

Oncogenic

Supports Oncogenicity

accepted

EID11013

A selective EZH2 inhibitor (EI1) was used to target the EZH2 Y641N mutation in DLBCL cell lines. EI1 treatment significantly inhibited proliferation in EZH2-mutated cells compared to lymphoma cells wi…

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
376217	-	-	—	Neoplasm	somatic	1	—	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

376217

—

Neoplasm

somatic

—

clinvar

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

Follicular Lymphoma2

EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G

(oncogenic)

Oncogenic

Supports Oncogenicity

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

Supports Sensitivity Response

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 disease4unmapped disease
EZH2 Y646N	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID9518 H3K27me3 (histone H3 Lys-27–specific trimethylation) level was higher in EZH2 (Y641N) bearing germinal center B-cell type DLBCL derived lymphoma cell lines and tumors than in wild-type cells. There wa… (full text at CIViC) PMID 21190999 · Yap et al., 2011 · Open in CIViC	civic
EZH2 Y646N	(functional)	Functional	D	Supports Loss Of Function	3	accepted	EID9520 A 3H methyl incorporation assay tested the function of EZH2 Y641N containing PRC2 complexes in vitro. It showed that Y641F/N PRC2 complexes had significantly decreased enzyme activity on unmethylated … (full text at CIViC) PMID 21190999 · Yap et al., 2011 · Open in CIViC	civic
EZH2 Y646N	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID11011 DLBCL cell lines carrying the EZH2 Y641N mutation (SU-DHL6 and Karpas422) were used to study the effect of EI1, a selective EZH2 inhibitor that functions by competing with the methyl group donor S-Ade… (full text at CIViC) PMID 23236167 · Qi et al., 2012 · Open in CIViC	civic
EZH2 Y646N	(functional)	Functional	D	Supports Gain Of Function	4	submitted	EID11050 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

Unmapped disease4unmapped disease

EZH2 Y646N

(functional)

Functional

Supports Gain Of Function

accepted

EID9518

H3K27me3 (histone H3 Lys-27–specific trimethylation) level was higher in EZH2 (Y641N) bearing germinal center B-cell type DLBCL derived lymphoma cell lines and tumors than in wild-type cells. There wa… (full text at CIViC)

PMID 21190999 · Yap et al., 2011 · Open in CIViC

civic

EZH2 Y646N

(functional)

Functional

Supports Loss Of Function

accepted

EID9520

A 3H methyl incorporation assay tested the function of EZH2 Y641N containing PRC2 complexes in vitro. It showed that Y641F/N PRC2 complexes had significantly decreased enzyme activity on unmethylated … (full text at CIViC)

PMID 21190999 · Yap et al., 2011 · Open in CIViC

civic

EZH2 Y646N

(functional)

Functional

Supports Gain Of Function

accepted

EID11011

DLBCL cell lines carrying the EZH2 Y641N mutation (SU-DHL6 and Karpas422) were used to study the effect of EI1, a selective EZH2 inhibitor that functions by competing with the methyl group donor S-Ade… (full text at CIViC)

PMID 23236167 · Qi et al., 2012 · Open in CIViC

civic

EZH2 Y646N

(functional)

Functional

Supports Gain Of Function

submitted

EID11050

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

Evidence by cancer (12 items)

Clinical significance (1)