Variant · Snv

TP53 R175H

CI-VAR-00003726Explore in graph →NP_000537.3:p.Arg175HisNM_000546.5:c.524G>AClinVar 12374 CIViC 116 rs28934578

Curated evidence

Evidence by cancer (13 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 1–13 of 13 evidence items across 6 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 R175H	EAP Protocol	Predictive	C	Supports Sensitivity Response	—	accepted	EID2310 In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC	civic
Malignant Breast Neoplasm2
TP53 R175H	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID389 Breast cancer patients who harbor R175H mutation have worse overall survival than those with wild type TP53, but have better prognosis than those with R248W mutation. PMID 16489069 · Olivier et al., 2006 ·

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
12374	Pathogenic	reviewed by expert panel	3	Li-Fraumeni syndrome 1; Hereditary cancer-predisposing syndrome; Malignant tumor of esophagus; Li-Fraumeni syndrome; Neoplasm; Ovarian neoplasm; Lip and oral cavity carcinoma; Squamous cell carcinoma of the head and neck; Familial cancer of breast; Colorectal cancer; Adrenocortical carcinoma, hereditary; Gastric cancer; TP53-related disorder; IDH-wildtype glioblastoma; Medulloblastoma SHH activated and TP53 mutant; Undifferentiated embryonal sarcoma of the liver; Neuroblastoma; Bone marrow failure syndrome 5; Astrocytoma IDH-mutant; Diffuse midline glioma, H3 K27M-mutant

Malignant Endometrial Neoplasm1
TP53 R175H	(oncogenic)	Oncogenic	D	Supports Oncogenicity	2	submitted	EID7429 A preclinical study was testing the neomorphic effects of TP53-R175H mutation. Multiple human endometrial cancer KLE cell lines were categorized into different groups: Untransfected cells, Vector (ve… (full text at CIViC) PMID 19917135 · Dong et al., 2009 · Open in CIViC	civic

Malignant Endometrial Neoplasm1

TP53 R175H

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID7429

A preclinical study was testing the neomorphic effects of TP53-R175H mutation. Multiple human endometrial cancer KLE cell lines were categorized into different groups: Untransfected cells, Vector (ve… (full text at CIViC)

PMID 19917135 · Dong et al., 2009 · Open in CIViC

civic

Malignant Neoplasm3
TP53 R175H	(oncogenic)	Oncogenic	D	Supports Oncogenicity	4	submitted	EID7119 Human mutant R175H p53 was stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression, resulting in viable cells. In contrast, p… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC	civic
TP53 R175H	MDM2 Inhibitor AMGMDS3	Predictive	D	Supports Resistance	3	accepted	EID4880 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 R175H	MDM2 Inhibitor AMGMDS3	Predictive	D	Supports Resistance	3	accepted	EID10074 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

Malignant Neoplasm3

TP53 R175H

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID7119

Human mutant R175H p53 was stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression, resulting in viable cells. In contrast, p… (full text at CIViC)

PMID 8099841 · Dittmer et al., 1993 · Open in CIViC

civic

TP53 R175H

MDM2 Inhibitor AMGMDS3

Predictive

Supports Resistance

accepted

EID4880

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 R175H

MDM2 Inhibitor AMGMDS3

Predictive

Supports Resistance

accepted

EID10074

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

civic

Sarcoma1
TP53 R175H OR TP53 H193R	Pazopanib + VorinostatCombination	Predictive	C	Supports Sensitivity Response	2	accepted	EID7540 In the phase I study of pazopanib and vorinostat in 36 patients with advanced solid tumors, detection of hotspot TP53 mutation was associated with a higher rate of SD ≥6 months/PR, longer median PFS (… (full text at CIViC) PMID 25669829 · Fu et al., 2015 · Open in CIViC	civic

Sarcoma1

TP53 R175H OR TP53 H193R

Pazopanib + VorinostatCombination

Predictive

Supports Sensitivity Response

accepted

EID7540

In the phase I study of pazopanib and vorinostat in 36 patients with advanced solid tumors, detection of hotspot TP53 mutation was associated with a higher rate of SD ≥6 months/PR, longer median PFS (… (full text at CIViC)

PMID 25669829 · Fu et al., 2015 · Open in CIViC

civic

Unmapped disease5unmapped disease
TP53 R175H	(functional)	Functional	D	Supports Loss Of Function	3	submitted	EID7106 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 R175H transcriptional activity, with colon… (full text at CIViC) PMID 27589690 · Billant et al., 2016 · Open in CIViC	civic
TP53 R175H	(functional)	Functional	D	Supports Dominant Negative	3	submitted	EID7112 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 R175H	(functional)	Functional	D	Supports Gain Of Function	4	submitted	EID7432 Several preclinical studies were testing the gain of function mechanisms of the TP53-R175H variant. Under the presence of the wild-type TP53 and mutant TP53 genes, there is a dominant-negative (antimo… (full text at CIViC) PMID 14743206 · Willis et al., 2004 · Open in CIViC	civic
TP53 R175H	(functional)	Functional	D	Does Not Support Neomorphic	4	submitted	EID7526 The R175H mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. R175H/- 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 R175H	(functional)	Functional	D	Supports Dominant Negative	3	accepted	EID10527 Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R175H 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 R175H

(functional)

Functional

Supports Loss Of Function

submitted

EID7106

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 R175H transcriptional activity, with colon… (full text at CIViC)

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

civic

TP53 R175H

(functional)

Functional

Supports Dominant Negative

submitted

EID7112

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 R175H

(functional)

Functional

Supports Gain Of Function

submitted

EID7432

Several preclinical studies were testing the gain of function mechanisms of the TP53-R175H variant. Under the presence of the wild-type TP53 and mutant TP53 genes, there is a dominant-negative (antimo… (full text at CIViC)

PMID 14743206 · Willis et al., 2004 · Open in CIViC

civic

TP53 R175H

(functional)

Functional

Does Not Support Neomorphic

submitted

EID7526

The R175H mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. R175H/- 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 R175H

(functional)

Functional

Supports Dominant Negative

accepted

EID10527

Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R175H 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