Variant · Snv

TP53 R273H

CI-VAR-00003801Explore in graph →NP_000537.3:p.Arg273HisNM_000546.5:c.818G>AClinVar 12366 CIViC 122 rs28934576

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 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
Glioblastoma1
TP53 R273H	Temozolomide	Predictive	D	Supports Resistance	3	submitted	EID7980 The glioblastoma U138 cell line possesses a TP53 R273H variant. This cell line initially exhibited resistance to temozolomide treatment, but a four-fold increase in chemosensitivity (IC50 127.79 ug/ml… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC	civic
Malignant Breast Neoplasm3
TP53 R273H	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID397 Breast cancer patients who harbor R273H 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
12366	Pathogenic	reviewed by expert panel	3	Li-Fraumeni syndrome 1; Thyroid gland undifferentiated (anaplastic) carcinoma; Hereditary cancer-predisposing syndrome; Lung adenocarcinoma; Neoplasm; Squamous cell carcinoma of the head and neck; Li-Fraumeni syndrome; Ovarian neoplasm; Colorectal cancer; Multiple myeloma; Malignant tumor of breast; Familial cancer of breast; Rhabdomyosarcoma; Gastric cancer; Breast and/or ovarian cancer; Adrenocortical carcinoma, hereditary; TP53-related disorder; Ewing sarcoma; Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; Diffuse midline glioma, H3 K27M-mutant; Desmoplastic small round cell tumor

Unmapped disease6unmapped disease
TP53 R273H	(functional)	Functional	D	Supports Loss Of Function	3	submitted	EID7111 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 R273H transcriptional activity, with colon… (full text at CIViC) PMID 27589690 · Billant et al., 2016 · Open in CIViC	civic
TP53 R273H	(functional)	Functional	D	Supports Dominant Negative	3	submitted	EID7117 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 R273H	(functional)	Functional	D	Supports Gain Of Function	4	submitted	EID7433 Several preclinical studies were testing the gain of function mechanisms of the TP53-R273H 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 R273H	(functional)	Functional	D	Does Not Support Neomorphic	4	accepted	EID7530 The R273H mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. R273H/- 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 R273H	(functional)	Functional	D	Supports Loss Of Function	2	submitted	EID9465 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 R273H	(functional)	Functional	D	Supports Dominant Negative	3	submitted	EID10536 Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R273H 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

Malignant Neoplasm2
TP53 R273H	(oncogenic)	Oncogenic	D	Supports Oncogenicity	4	submitted	EID7121 Plasmids harboring human TP53 with or without an R273H mutation were stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression.… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC	civic
TP53 R273H	MDM2 Inhibitor AMGMDS3	Predictive	D	Supports Resistance	4	accepted	EID4882 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