Variant · Snv

TP53 Y220C

CI-VAR-00004783Explore in graph →NP_000537.3:p.Tyr220CysNM_000546.5:c.659A>GClinVar 127819 CIViC 922 rs121912666

Curated evidence

Evidence by cancer (10 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 1–10 of 10 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
Gastric Carcinoma1
TP53 Y220C	Cisplatin + Etoposide + MitomycinCombination	Predictive	C	Supports Sensitivity Response	3	accepted	EID2306 A male patient taking part in a 25 patient gastric cancer trial was diagnosed at age 50, harbored a TP53 mutation and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric … (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC	civic
Malignant Breast Neoplasm1
TP53 Y220C	Bortezomib	Predictive	C	Supports Sensitivity Response	3	submitted	EID6172 TP53 Y220C is known to destabilize p53 and down-regulate p53-mediated apoptosis. The success of bortezomib may be explained by the previously reported up-regulation of caspase-mediated apoptosis, whic…

ClinVar

Clinical significance (1)

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

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
127819	Pathogenic	reviewed by expert panel	3	Hereditary cancer-predisposing syndrome; Li-Fraumeni syndrome; Squamous cell carcinoma of the head and neck; Ovarian neoplasm; Li-Fraumeni syndrome 1; B-cell chronic lymphocytic leukemia; Breast carcinoma; Gastric cancer; TP53-related disorder; Adrenal cortex carcinoma; Adrenocortical carcinoma, hereditary; Neoplasm; Familial cancer of breast; Squamous cell lung carcinoma; Adenocarcinoma of the large intestine; Ovarian mucinous adenocarcinoma; Malignant tumor of esophagus; Malignant tumor of urinary bladder; Lung cancer; Embryonal rhabdomyosarcoma; Diffuse midline glioma, H3 K27M-mutant; Pancreatic adenocarcinoma; Colon adenocarcinoma; Sarcoma; Glioma susceptibility 1; Astrocytoma IDH-mutant

Malignant Neoplasm3
TP53 Y220C	MDM2 Inhibitor AMGMDS3	Predictive	D	Supports Resistance	4	accepted	EID4884 Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC	civic
TP53 Y220C	Rezatapopt	Predictive	C	Supports Sensitivity Response	3	submitted	EID12297 Rezatapopt demonstrated clinical efficacy in the PYNNACLE Phase 1 dose-escalation study (NCT04585750), showing promising responses in two heavily pre-treated patients with solid tumors. A patient with… (full text at CIViC) PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC	civic
TP53 Y220C	Rezatapopt	Predictive	D	Supports Sensitivity Response	3	submitted	EID12296 Four TP53 reactivator compounds—PC09859, PC10709, PC14374, and rezatapopt (PC14586)—were tested for their ability to restore wild-type (WT) TP53 function in TP53 Y220C-mutated cells. ELISA assays in N… (full text at CIViC) PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC	civic

Malignant Neoplasm3

TP53 Y220C

MDM2 Inhibitor AMGMDS3

Predictive

Supports Resistance

accepted

EID4884

Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC)

PMID 25730903 · Saiki et al., 2015 · Open in CIViC

civic

TP53 Y220C

Rezatapopt

Predictive

Supports Sensitivity Response

submitted

EID12297

Rezatapopt demonstrated clinical efficacy in the PYNNACLE Phase 1 dose-escalation study (NCT04585750), showing promising responses in two heavily pre-treated patients with solid tumors. A patient with… (full text at CIViC)

PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC

civic

TP53 Y220C

Rezatapopt

Predictive

Supports Sensitivity Response

submitted

EID12296

Four TP53 reactivator compounds—PC09859, PC10709, PC14374, and rezatapopt (PC14586)—were tested for their ability to restore wild-type (WT) TP53 function in TP53 Y220C-mutated cells. ELISA assays in N… (full text at CIViC)

PMID 39945593 · Puzio-Kuter et al., 2025 · Open in CIViC

civic

Unmapped disease5unmapped disease
TP53 Y220C	(functional)	Functional	D	Does Not Support Loss Of Function	3	accepted	EID7107 A reporter assay in FASAY yeast strain using the ADE2 gene under control of the p-21 or RGC p53 response elements was performed to assay p53 hotspot mutation Y220C transcriptional activity, with colon… (full text at CIViC) PMID 27589690 · Billant et al., 2016 · Open in CIViC	civic
TP53 Y220C	(functional)	Functional	D	Does Not Support Dominant Negative	3	submitted	EID7113 A reporter assay in FASAY yeast strain using the ADE2 gene under control of a p53 response element was performed, with colony color (white vs red) as readout for p53 transactivation activity, where wt… (full text at CIViC) PMID 27589690 · Billant et al., 2016 · Open in CIViC	civic
TP53 Y220C	(functional)	Functional	D	Does Not Support Neomorphic	4	accepted	EID7527 The Y220C mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. Y220C/- cells showed resistance to chemotherapeutic agents and failure to induce p21, indicating disruption o… (full text at CIViC) PMID 31395785 · Boettcher et al., 2019 · Open in CIViC	civic
TP53 Y220C	(functional)	Functional	D	Supports Loss Of Function	2	submitted	EID9506 Fifty missense mutations identified in sporadic breast cancer were assessed for qualitative and quantitative changes in their ability to transactivate from 11 human promoter response elements (REs) in… (full text at CIViC) PMID 20407015 · Jordan et al., 2010 · Open in CIViC	civic
TP53 Y220C	(functional)	Functional	D	Does Not Support Dominant Negative	3	submitted	EID10571 Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant Y220C originally identified in anaplastic astrocytoma. Should the mutant be dominant-negative (DN), TP53 will not bind and tr… (full text at CIViC) PMID 10519380 · Marutani et al., 1999 · Open in CIViC	civic

Unmapped disease5unmapped disease

TP53 Y220C

(functional)

Functional

Does Not Support Loss Of Function

accepted

EID7107

A reporter assay in FASAY yeast strain using the ADE2 gene under control of the p-21 or RGC p53 response elements was performed to assay p53 hotspot mutation Y220C transcriptional activity, with colon… (full text at CIViC)

PMID 27589690 · Billant et al., 2016 · Open in CIViC

civic

TP53 Y220C

(functional)

Functional

Does Not Support Dominant Negative

submitted

EID7113

A reporter assay in FASAY yeast strain using the ADE2 gene under control of a p53 response element was performed, with colony color (white vs red) as readout for p53 transactivation activity, where wt… (full text at CIViC)

PMID 27589690 · Billant et al., 2016 · Open in CIViC

civic

TP53 Y220C

(functional)

Functional

Does Not Support Neomorphic

accepted

EID7527

The Y220C mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. Y220C/- cells showed resistance to chemotherapeutic agents and failure to induce p21, indicating disruption o… (full text at CIViC)

PMID 31395785 · Boettcher et al., 2019 · Open in CIViC

civic

TP53 Y220C

(functional)

Functional

Supports Loss Of Function

submitted

EID9506

Fifty missense mutations identified in sporadic breast cancer were assessed for qualitative and quantitative changes in their ability to transactivate from 11 human promoter response elements (REs) in… (full text at CIViC)

PMID 20407015 · Jordan et al., 2010 · Open in CIViC

civic

TP53 Y220C

(functional)

Functional

Does Not Support Dominant Negative

submitted

EID10571

Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant Y220C originally identified in anaplastic astrocytoma. Should the mutant be dominant-negative (DN), TP53 will not bind and tr… (full text at CIViC)

PMID 10519380 · Marutani et al., 1999 · Open in CIViC

civic