Variant · Snv

TP53 R248Q

CI-VAR-00003784Explore in graph →NP_000537.3:p.Arg248GlnNM_000546.5:c.743G>AClinVar 12356 CIViC 117 rs11540652

Curated evidence

Evidence by cancer (12 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 1–12 of 12 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
Lymphoma1
TP53 R248Q	(predisposing)	Predisposing	D	Supports Predisposition	4	accepted	EID7161 In mouse models, the R248Q variant had accelerated onset of all tumor types and accelerated death rate. Endogenous R248Q proteins are devoid of several important wildtype tp53 tumor-suppressor functio… (full text at CIViC) PMID 23538418 · Hanel et al., 2013 · Open in CIViC	civic
Malignant Breast Neoplasm2
TP53 R248Q	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID390 Breast cancer patients who harbor a R248Q mutation (N=18) have worse overall survival than those with wild type TP53 (N=1460), but have better prognosis than those with a R248W mutation (N=8). 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
12356	Pathogenic	reviewed by expert panel	3	Li-Fraumeni syndrome 1; Hereditary cancer-predisposing syndrome; Li-Fraumeni syndrome; Sarcoma; Neoplasm; Multiple myeloma; Ovarian neoplasm; Lymphoma; Familial cancer of breast; Breast carcinoma; Ductal carcinoma in situ; Lip and oral cavity carcinoma; Rhabdomyosarcoma; Adrenal cortex carcinoma; Gastric cancer; Malignant tumor of urinary bladder; Adrenocortical carcinoma, hereditary; Hereditary breast ovarian cancer syndrome; Colorectal cancer; TP53-related disorder; Embryonal rhabdomyosarcoma; Diffuse midline glioma, H3 K27M-mutant; Nasopharyngeal carcinoma; Anaplastic/large cell medulloblastoma; Bone marrow failure syndrome 5; Medulloblastoma WNT activated; Adenocarcinoma of the large intestine; Embryonal tumor with multilayered rosettes

Unmapped disease6unmapped disease
TP53 R248Q	(functional)	Functional	D	Supports Loss Of Function	3	submitted	EID7109 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 R248Q transcriptional activity, with colon… (full text at CIViC) PMID 27589690 · Billant et al., 2016 · Open in CIViC	civic
TP53 R248Q	(functional)	Functional	D	Supports Dominant Negative	3	accepted	EID7115 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 R248Q	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID7442 Several preclinical studies were testing how TP53-R248Q variant induces over-expression of HER2 in various types of cancer cells. Through RT-qPCR, OVCAR-3 cell line (harboring the TP53-R248Q variant)… (full text at CIViC) PMID 29970031 · Román-Rosales et al., 2018 · Open in CIViC	civic
TP53 R248Q	(functional)	Functional	D	Supports Dominant Negative	4	accepted	EID7525 CRISPR-Cas9 editing was used to create five isogenic MOLM13-TP53 AML cell lines with combinations of wild-type, mutant, and null TP53 alleles at the endogenous locus: p53+/+, p53+/-, p53-/-, R248Q/+, … (full text at CIViC) PMID 31395785 · Boettcher et al., 2019 · Open in CIViC	civic
TP53 R248Q	(functional)	Functional	D	Does Not Support Neomorphic	4	accepted	EID7529 The R248Q mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. R248Q/- 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 R248Q	(functional)	Functional	D	Supports Dominant Negative	3	submitted	EID10535 Yeast strain yIG397 was cultured to express both wild-type (WT) and mutant R248Q 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