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NM_000546.6(TP53):c.818G>A (p.Arg273His)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
56
First in ClinVar:
Apr 8, 2013
Most recent Submission:
Apr 15, 2023
Last evaluated:
Aug 28, 2019
Accession:
VCV000012366.51
Variation ID:
12366
Description:
single nucleotide variant
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NM_000546.6(TP53):c.818G>A (p.Arg273His)

Allele ID
27405
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7673802 (GRCh38) GRCh38 UCSC
17: 7577120 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000546.6:c.818G>A MANE Select NP_000537.3:p.Arg273His missense
NM_000546.5(TP53):c.818G>A
NM_001126112.3:c.818G>A NP_001119584.1:p.Arg273His missense
... more HGVS
Protein change
R273H, R141H, R234H, R114H
Other names
p.R273H:CGT>CAT
Canonical SPDI
NC_000017.11:7673801:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
1000 Genomes Project 0.00020
Links
ClinGen: CA000434
UniProtKB: P04637#VAR_005995
OMIM: 191170.0020
dbSNP: rs28934576
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 reviewed by expert panel Aug 28, 2019 RCV000463420.12
Pathogenic/Likely pathogenic 7 criteria provided, multiple submitters, no conflicts Sep 1, 2022 RCV000013163.29
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Aug 24, 2021 RCV000115738.13
Pathogenic 6 criteria provided, multiple submitters, no conflicts Apr 29, 2022 RCV000254693.19
Pathogenic 2 criteria provided, single submitter - RCV000422097.3
Pathogenic 2 criteria provided, single submitter Jun 6, 2022 RCV000431361.3
Pathogenic 1 criteria provided, single submitter Mar 14, 2022 RCV002476955.1
Pathogenic 1 no assertion criteria provided Jan 1, 1993 RCV000013164.6
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000424109.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000419960.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000418930.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000422733.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000424218.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000439513.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000440815.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000424833.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000443907.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000423826.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000424627.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000428779.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000429822.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000430161.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000433409.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000435547.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000434044.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000437210.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000436207.2
Likely pathogenic 1 no assertion criteria provided Jul 14, 2015 RCV000441169.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000440474.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000444851.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000444900.2
Pathogenic/Likely pathogenic 2 no assertion criteria provided Mar 19, 2021 RCV000785345.4
Pathogenic 1 no assertion criteria provided Sep 1, 2020 RCV001257517.2
Pathogenic 1 no assertion criteria provided Mar 19, 2021 RCV001527470.2
Pathogenic 1 no assertion criteria provided - RCV001358389.2
Pathogenic 1 no assertion criteria provided Mar 19, 2021 RCV001527484.2
Pathogenic 1 no assertion criteria provided Jul 1, 2021 RCV003162246.1
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TP53 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2836 2931

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Pathogenic
(Aug 28, 2019)
reviewed by expert panel
Method: curation
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin: germline
ClinGen TP53 Variant Curation Expert Panel,ClinGen
FDA Recognized Database
Accession: SCV001142550.1
First in ClinVar: Jan 12, 2020
Last updated: Jan 12, 2020
Publications:
PubMed (9)
Other databases
https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8d32df42-16ac-41f2-9bf1-e2b9ce206190
Comment:
This variant is within a codon that is an established hotspot in the TP53 gene (PM1; PMID: 2046748). This variant has a BayesDel score > … (more)
Pathogenic
(Jan 12, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Color Diagnostics, LLC DBA Color Health
Accession: SCV001735236.1
First in ClinVar: Jun 19, 2021
Last updated: Jun 19, 2021
Comment:
This missense variant replaces arginine with histidine at codon 273 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant … (more)
Pathogenic
(Mar 18, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605425.2
First in ClinVar: Sep 30, 2017
Last updated: Jan 08, 2022
Comment:
The TP53 c.818G>A, p.Arg273His variant (rs28934576), has been reported in multiple patients diagnosed with Li-Fraumeni syndrome (Curry 2011, Khayat 2004, Malkin 1992, Park 2016, Schlegelberger … (more)
Pathogenic
(Sep 01, 2022)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin: germline
3billion
Accession: SCV002572762.1
First in ClinVar: Sep 17, 2022
Last updated: Sep 17, 2022
Publications:
PubMed (9)
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). It is located in a mutational hot … (more)
Clinical Features:
Osteosarcoma (present)
Zygosity: 1 Single Heterozygote
Pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Affected status: unknown
Allele origin: unknown
Mendelics
Accession: SCV000839110.2
First in ClinVar: Oct 10, 2018
Last updated: Dec 11, 2022
Likely pathogenic
(Feb 22, 2017)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: unknown
Counsyl
Accession: SCV000677727.2
First in ClinVar: Oct 19, 2014
Last updated: Dec 24, 2022
Publications:
PubMed (12)
Pathogenic
(Jun 06, 2022)
criteria provided, single submitter
Method: research
Lung adenocarcinoma
Affected status: yes
Allele origin: somatic
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
Accession: SCV003806294.1
First in ClinVar: Mar 04, 2023
Last updated: Mar 04, 2023
Number of individuals with the variant: 1
Pathogenic
(Apr 29, 2022)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000149647.15
First in ClinVar: May 17, 2014
Last updated: Mar 04, 2023
Comment:
Not observed at a significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity … (more)
Pathogenic
(Feb 09, 2017)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Affected status: unknown
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697450.1
First in ClinVar: Dec 26, 2017
Last updated: Dec 26, 2017
Publications:
PubMed (3)
PubMed: 92424562558400822899716
Comment:
Variant summary: The TP53 c.818G>A (p.Arg273His) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. … (more)
Likely pathogenic
(Jan 01, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin: germline
GeneKor MSA
Accession: SCV000821786.2
First in ClinVar: Oct 10, 2018
Last updated: May 04, 2020
Comment:
This sequence change replaces Arginine with Histidine at codon 273 of the TP53 protein. The arginine residue is highly conserved among species and is located … (more)
Pathogenic
(-)
criteria provided, single submitter
Method: case-control
Squamous cell carcinoma of the head and neck
Affected status: yes
Allele origin: somatic
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450494.1
First in ClinVar: Dec 12, 2020
Last updated: Dec 12, 2020
Publications:
PubMed (1)
PubMed: 30816478
Age: 50-59 years
Sex: male
Geographic origin: Sri Lanka
Pathogenic
(Dec 15, 2020)
criteria provided, single submitter
Method: research
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin: germline
Department of Pediatrics,Memorial Sloan Kettering Cancer Center
Accession: SCV001478190.1
First in ClinVar: Jun 19, 2021
Last updated: Jun 19, 2021
Publications:
PubMed (1)
PubMed: 28873162
Pathogenic
(Jun 17, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762058.1
First in ClinVar: Jul 31, 2021
Last updated: Jul 31, 2021
Clinical Features:
Breast carcinoma (present)
Sex: female
Pathogenic
(Apr 26, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000602280.2
First in ClinVar: Sep 28, 2017
Last updated: Jan 01, 2022
Publications:
PubMed (10)
Pathogenic
(Nov 23, 2021)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin: germline
Centogene AG - the Rare Disease Company
Accession: SCV002059231.1
First in ClinVar: Jan 15, 2022
Last updated: Jan 15, 2022
Pathogenic
(Apr 03, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: yes
Allele origin: germline
Genetic Services Laboratory, University of Chicago
Accession: SCV002072052.1
First in ClinVar: Jan 29, 2022
Last updated: Jan 29, 2022
Comment:
DNA sequence analysis of the TP53 gene demonstrated a sequence change, c.818G>A, in exon 8 that results in an amino acid change, p.Arg273His. This sequence … (more)
Pathogenic
(Aug 24, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Ambry Genetics
Accession: SCV000186052.8
First in ClinVar: Aug 06, 2014
Last updated: Nov 29, 2022
Publications:
PubMed (9)
Comment:
The p.R273H pathogenic mutation (also known as c.818G>A), located in coding exon 7 of the TP53 gene, results from a G to A substitution at … (more)
Number of individuals with the variant: 1
Pathogenic
(Sep 10, 2021)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: germline
New York Genome Center
Accession: SCV002764339.1
First in ClinVar: Dec 17, 2022
Last updated: Dec 17, 2022
Publications:
PubMed (7)
Comment:
The c.818G>A, p.Arg273His missense variant in TP53 has been reported in several individuals meeting classic Li-Fraumeni or Chompret criteria,occurring de novo in at least one … (more)
Clinical Features:
Hepatic steatosis (present) , Type 2 diabetes mellitus (present) , Hyperlipidemia (present)
Zygosity: 1 Single Heterozygote
Secondary finding: yes
Pathogenic
(Mar 14, 2022)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Colorectal cancer
Hepatocellular carcinoma
Glioma susceptibility 1
Li-Fraumeni syndrome 1
Adrenocortical carcinoma, hereditary
Bone osteosarcoma
Carcinoma of pancreas
Choroid plexus papilloma
Nasopharyngeal carcinoma
Basal cell carcinoma, susceptibility to, 7
Bone marrow failure syndrome 5
Affected status: unknown
Allele origin: unknown
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611327.2
First in ClinVar: Nov 11, 2017
Last updated: Dec 31, 2022
Pathogenic
(Oct 25, 2022)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV000545317.9
First in ClinVar: Apr 17, 2017
Last updated: Feb 07, 2023
Publications:
PubMed (10)
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 273 of the TP53 protein (p.Arg273His). … (more)
Pathogenic
(Jan 01, 1993)
no assertion criteria provided
Method: literature only
LI-FRAUMENI SYNDROME 1
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033410.2
First in ClinVar: Apr 04, 2013
Last updated: Apr 08, 2013
Publications:
PubMed (2)
PubMed: 15651448423216
Comment on evidence:
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was … (more)
Pathogenic
(Jan 01, 1993)
no assertion criteria provided
Method: literature only
THYROID CARCINOMA, ANAPLASTIC, SOMATIC
Affected status: not provided
Allele origin: somatic
OMIM
Accession: SCV000033411.2
First in ClinVar: Apr 04, 2013
Last updated: Apr 08, 2013
Publications:
PubMed (2)
PubMed: 15651448423216
Comment on evidence:
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was … (more)
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Acute myeloid leukemia
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504664.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (4)
PubMed: 24381225246413752448741326619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Prostate adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504665.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Malignant melanoma of skin
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504666.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Hepatocellular carcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504667.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neoplasm of brain
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504668.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Brainstem glioma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504669.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neoplasm of the large intestine
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504670.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Multiple myeloma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504671.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Carcinoma of esophagus
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504672.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Breast neoplasm
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504673.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (3)
PubMed: 95690501648906926619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Adrenal cortex carcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504674.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504675.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Squamous cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504676.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Ovarian serous cystadenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504677.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504678.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504679.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Transitional cell carcinoma of the bladder
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504680.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Medulloblastoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504681.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
B-cell chronic lymphocytic leukemia
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504682.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
None
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504683.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(Jul 14, 2015)
no assertion criteria provided
Method: literature only
Neoplasm
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504684.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 25157968
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Uterine carcinosarcoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504685.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Affected status: unknown
Allele origin: unknown
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV000692068.1
First in ClinVar: Feb 19, 2018
Last updated: Feb 19, 2018
Pathogenic
(Sep 01, 2020)
no assertion criteria provided
Method: provider interpretation
Rhabdomyosarcoma
Affected status: yes
Allele origin: germline
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434343.1
First in ClinVar: Oct 03, 2020
Last updated: Oct 03, 2020
Publications:
PubMed (1)
PubMed: 33372952
Pathogenic
(Jul 24, 2014)
no assertion criteria provided
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: germline
Pathway Genomics
Accession: SCV000190004.1
First in ClinVar: Oct 19, 2014
Last updated: Oct 19, 2014
Publications:
PubMed (6)
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Pancreatic adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504661.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
None
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504662.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504663.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (1)
PubMed: 26619011
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A
Likely pathogenic
(Dec 01, 2018)
no assertion criteria provided
Method: research
Neoplasm of ovary
Affected status: yes
Allele origin: somatic
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923913.1
First in ClinVar: Jun 17, 2019
Last updated: Jun 17, 2019

Observation 1:

Observation 2:

Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Malignant tumor of breast
Affected status: yes
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001554107.1
First in ClinVar: Apr 13, 2021
Last updated: Apr 13, 2021
Comment:
The TP53 p.Arg273His variant was identified in 2 of 942 proband chromosomes (frequency: 0.002) from individuals or families with Li Fraumeni Syndrome or thyroid cancer … (more)
Number of individuals with the variant: 1
Pathogenic
(Mar 19, 2021)
no assertion criteria provided
Method: clinical testing
Multiple myeloma
Colorectal cancer
Affected status: yes
Allele origin: somatic
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738487.1
First in ClinVar: Jun 26, 2021
Last updated: Jun 26, 2021
Comment:
Related to multiple myeloma
Secondary finding: yes
Pathogenic
(Mar 19, 2021)
no assertion criteria provided
Method: clinical testing
Neoplasm of ovary
Affected status: no
Allele origin: somatic
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738490.1
First in ClinVar: Jun 26, 2021
Last updated: Jun 26, 2021
Secondary finding: yes
Pathogenic
(Mar 19, 2021)
no assertion criteria provided
Method: clinical testing
Familial cancer of breast
Affected status: no
Allele origin: somatic
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738505.1
First in ClinVar: Jun 26, 2021
Last updated: Jun 26, 2021
Secondary finding: yes
Pathogenic
(Jul 01, 2021)
no assertion criteria provided
Method: research
Gastric cancer
Affected status: unknown
Allele origin: germline
Laboratory for Genotyping Development, RIKEN
Accession: SCV002758479.1
First in ClinVar: Apr 15, 2023
Last updated: Apr 15, 2023
Publications:
PubMed (1)
PubMed: 36988593

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. Usui Y The New England journal of medicine 2023 PMID: 36988593
Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group. Li H Journal of the National Cancer Institute 2021 PMID: 33372952
Identifying sequence variants contributing to hereditary breast and ovarian cancer in BRCA1 and BRCA2 negative breast and ovarian cancer patients. Jarhelle E Scientific reports 2019 PMID: 31882575
Nucleotide variants and protein expression of TP53 in a Sri Lankan cohort of patients with head and neck cancer. Manoharan V Molecular medicine reports 2019 PMID: 30816478
Mutational processes shape the landscape of TP53 mutations in human cancer. Giacomelli AO Nature genetics 2018 PMID: 30224644
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. Kotler E Molecular cell 2018 PMID: 29979965
The landscape of genomic alterations across childhood cancers. Gröbner SN Nature 2018 PMID: 29489754
Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. Mandelker D JAMA 2017 PMID: 28873162
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Kline CN Neuro-oncology 2017 PMID: 28453743
Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome. Park KJ Annals of laboratory medicine 2016 PMID: 27374712
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Chang MT Nature biotechnology 2016 PMID: 26619011
Identification of Medically Actionable Secondary Findings in the 1000 Genomes. Olfson E PloS one 2015 PMID: 26332594
A child with Li-Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies. Schlegelberger B Pediatric blood & cancer 2015 PMID: 25787918
Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study. Wasserman JD Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 PMID: 25584008
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. MacConaill LE The Journal of molecular diagnostics : JMD 2014 PMID: 25157968
Mutants TP53 p.R273H and p.R273C but not p.R273G enhance cancer cell malignancy. Li J Human mutation 2014 PMID: 24677579
Prognostic significance of TP53 mutations and single nucleotide polymorphisms in acute myeloid leukemia: a case series and literature review. Zeichner SB Asian Pacific journal of cancer prevention : APJCP 2014 PMID: 24641375
Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Kihara R Leukemia 2014 PMID: 24487413
Haploinsufficiency of del(5q) genes, Egr1 and Apc, cooperate with Tp53 loss to induce acute myeloid leukemia in mice. Stoddart A Blood 2014 PMID: 24381225
The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis. Leroy B Nucleic acids research 2013 PMID: 23161690
BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Pennington KP Cancer 2013 PMID: 22811390
Mutant p53R273H attenuates the expression of phase 2 detoxifying enzymes and promotes the survival of cells with high levels of reactive oxygen species. Kalo E Journal of cell science 2012 PMID: 22899716
Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Melhem-Bertrandt A Cancer 2012 PMID: 21761402
Gastric cancer in individuals with Li-Fraumeni syndrome. Masciari S Genetics in medicine : official journal of the American College of Medical Genetics 2011 PMID: 21552135
Association of germline or somatic TP53 missense mutation with oncogene amplification in tumors developed in patients with Li-Fraumeni or Li-Fraumeni-like syndrome. Sugawara W Genes, chromosomes & cancer 2011 PMID: 21484931
Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Monti P Molecular cancer research : MCR 2011 PMID: 21343334
Sebaceous gland carcinoma of the eyelid masquerading as a cutaneous horn in Li--Fraumeni syndrome. Baumüller S The British journal of ophthalmology 2011 PMID: 20693561
The tumor suppressor p53: from structures to drug discovery. Joerger AC Cold Spring Harbor perspectives in biology 2010 PMID: 20516128
Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation. Malcikova J Biological chemistry 2010 PMID: 20128691
Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. Bougeard G Journal of medical genetics 2008 PMID: 18511570
p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells. Dong P Clinical & experimental metastasis 2007 PMID: 17636407
Transcriptional functionality of germ line p53 mutants influences cancer phenotype. Monti P Clinical cancer research : an official journal of the American Association for Cancer Research 2007 PMID: 17606709
EGFR-mutant lung adenocarcinoma in a patient with Li-Fraumeni syndrome. Bemis LT The Lancet. Oncology 2007 PMID: 17540308
The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Olivier M Clinical cancer research : an official journal of the American Association for Cancer Research 2006 PMID: 16489069
Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Wong P Gastroenterology 2006 PMID: 16401470
The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. Siddiqui R Familial cancer 2005 PMID: 15951970
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Olive KP Cell 2004 PMID: 15607980
Rhabdomyosarcoma, osteosarcoma, and adrenocortical carcinoma in a child with a germline p53 mutation. Khayat CM Pediatric blood & cancer 2004 PMID: 15390294
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Kato S Proceedings of the National Academy of Sciences of the United States of America 2003 PMID: 12826609
Prediction of pathogenic mutations in patients with early-onset breast cancer by family history. Lalloo F Lancet (London, England) 2003 PMID: 12672316
P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Chompret A British journal of cancer 2000 PMID: 10864200
Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. Berns EM British journal of cancer 1998 PMID: 9569050
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Varley JM Cancer research 1997 PMID: 9242456
A simple p53 functional assay for screening cell lines, blood, and tumors. Flaman JM Proceedings of the National Academy of Sciences of the United States of America 1995 PMID: 7732013
High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. Fagin JA The Journal of clinical investigation 1993 PMID: 8423216
Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. Malkin D The New England journal of medicine 1992 PMID: 1565144
http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8d32df42-16ac-41f2-9bf1-e2b9ce206190 - - - -

Text-mined citations for rs28934576...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 04, 2023