Variant · Snv

TP53 R273C

CI-VAR-00003799Explore in graph →NP_000537.3:p.Arg273CysNM_000546.5:c.817C>TClinVar 43594 CIViC 121 rs121913343

Curated evidence

Evidence by cancer (9 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 1–9 of 9 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
Gastric Carcinoma1
TP53 R273C	Cisplatin + Etoposide + MitomycinCombination	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID2292 A female patient taking part in a 25 patient gastric cancer trial was diagnosed at age 46, and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric Cancer Response Score w… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC	civic
Malignant Breast Neoplasm2
TP53 R273C	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID395 Breast cancer patients who harbor R273C mutation have worse overall survival than those with wild type TP53, but have better prognosis than those with R248W mutation.

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
43594	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Hereditary cancer-predisposing syndrome; Li-Fraumeni syndrome 1; Prostate cancer; Li-Fraumeni syndrome; Neoplasm; Ovarian neoplasm; Adrenocortical carcinoma, hereditary; Multiple myeloma; TP53-related disorder; Embryonal rhabdomyosarcoma; Neuroblastoma; Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; Astrocytoma IDH-mutant; Medulloblastoma WNT activated; Primary intracranial sarcoma, DICER1-mutant; Adenocarcinoma of the large intestine; Diffuse midline glioma, H3 K27M-mutant

Malignant Colorectal Neoplasm1
TP53 R273C OR TP53 G245S OR TP53 R213*	Pazopanib + VorinostatCombination	Predictive	C	Supports Sensitivity Response	2	accepted	EID12732 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

Malignant Colorectal Neoplasm1

TP53 R273C OR TP53 G245S OR TP53 R213*

Pazopanib + VorinostatCombination

Predictive

Supports Sensitivity Response

accepted

EID12732

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

Malignant Neoplasm1
TP53 R273C	MDM2 Inhibitor AMGMDS3	Predictive	D	Supports Resistance	4	accepted	EID4881 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 Neoplasm1

TP53 R273C

MDM2 Inhibitor AMGMDS3

Predictive

Supports Resistance

accepted

EID4881

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

Unmapped disease4unmapped disease
TP53 R273C	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID7443 Several preclinical studies were testing how TP53-R273C variant induces over-expression of HER2 in various types of cancer cells. Through RT-qPCR, CC3A cells (harboring the TP53-R273C variant) were s… (full text at CIViC) PMID 29970031 · Román-Rosales et al., 2018 · Open in CIViC	civic
TP53 R273C	(functional)	Functional	D	Supports Loss Of Function	2	submitted	EID9464 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 in a yea… (full text at CIViC) PMID 20407015 · Jordan et al., 2010 · Open in CIViC	civic
TP53 R273C	(functional)	Functional	D	Supports Dominant Negative	3	accepted	EID10256 A set of previously characterized p53 mutants was tested in the yeast assay to understand their transdominant potential (dominant negative). Each mutant was expressed equally with the wild-type p53. T… (full text at CIViC) PMID 11896595 · Monti et al., 2002 · Open in CIViC	civic
TP53 R273C	(functional)	Functional	D	Supports Dominant Negative	3	submitted	EID10537 Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R273C originally identified in glioblastoma. Should the mutant be dominant-negative (DN), TP53 will not bind and transactivat… (full text at CIViC) PMID 10519380 · Marutani et al., 1999 · Open in CIViC	civic

Unmapped disease4unmapped disease

TP53 R273C

(functional)

Functional

Supports Gain Of Function

submitted

EID7443

Several preclinical studies were testing how TP53-R273C variant induces over-expression of HER2 in various types of cancer cells. Through RT-qPCR, CC3A cells (harboring the TP53-R273C variant) were s… (full text at CIViC)

PMID 29970031 · Román-Rosales et al., 2018 · Open in CIViC

civic

TP53 R273C

(functional)

Functional

Supports Loss Of Function

submitted

EID9464

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 in a yea… (full text at CIViC)

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

civic

TP53 R273C

(functional)

Functional

Supports Dominant Negative

accepted

EID10256

A set of previously characterized p53 mutants was tested in the yeast assay to understand their transdominant potential (dominant negative). Each mutant was expressed equally with the wild-type p53. T… (full text at CIViC)

PMID 11896595 · Monti et al., 2002 · Open in CIViC

civic

TP53 R273C

(functional)

Functional

Supports Dominant Negative

submitted

EID10537

Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R273C originally identified in glioblastoma. Should the mutant be dominant-negative (DN), TP53 will not bind and transactivat… (full text at CIViC)

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

civic