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NM_000546.6(TP53):c.743G>A (p.Arg248Gln)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
56
First in ClinVar:
Apr 4, 2013
Most recent Submission:
Jun 18, 2022
Last evaluated:
Aug 28, 2019
Accession:
VCV000012356.32
Variation ID:
12356
Description:
single nucleotide variant
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NM_000546.6(TP53):c.743G>A (p.Arg248Gln)

Allele ID
27395
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7674220 (GRCh38) GRCh38 UCSC
17: 7577538 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000546.6:c.743G>A MANE Select NP_000537.3:p.Arg248Gln missense
NM_000546.5(TP53):c.743G>A
NM_001126112.3:c.743G>A NP_001119584.1:p.Arg248Gln missense
... more HGVS
Protein change
R248Q, R116Q, R209Q, R89Q
Other names
p.R248Q:CGG>CAG
Canonical SPDI
NC_000017.11:7674219:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Links
ClinGen: CA000387
UniProtKB: P04637#VAR_005983
OMIM: 191170.0010
dbSNP: rs11540652
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 RCV000197114.13
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Feb 17, 2022 RCV000013150.24
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Apr 5, 2021 RCV000115736.16
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Dec 3, 2021 RCV000235221.13
Pathogenic 1 criteria provided, single submitter Oct 31, 2018 RCV000763417.2
Pathogenic 2 criteria provided, single submitter - RCV001270275.3
Pathogenic 1 no assertion criteria provided Jun 1, 2014 RCV000148913.3
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000420727.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000421194.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000426359.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000417916.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000432778.2
Likely pathogenic 1 no assertion criteria provided Jul 14, 2015 RCV000426606.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000435533.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000419135.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000420303.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000437291.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000421893.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000438410.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000426233.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000439963.2
Likely pathogenic 2 no assertion criteria provided Aug 31, 2019 RCV000424869.3
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000433424.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000428591.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000427709.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000437518.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000445244.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000430513.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000432587.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000437935.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000444656.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000441226.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000445235.2
Likely pathogenic 1 no assertion criteria provided Jul 25, 2019 RCV000790860.2
Likely pathogenic 1 no assertion criteria provided Dec 1, 2018 RCV000785344.3
Pathogenic 1 no assertion criteria provided Apr 30, 2019 RCV001255671.2
Pathogenic 1 no assertion criteria provided Sep 1, 2020 RCV001257519.2
Pathogenic 1 no assertion criteria provided Mar 19, 2021 RCV001527465.2
Pathogenic 1 no assertion criteria provided Aug 8, 2021 RCV001554245.2
Pathogenic 1 no assertion criteria provided Apr 12, 2016 RCV001789749.2
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
2462 2544

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: SCV001142549.1
First in ClinVar: Jan 12, 2020
Last updated: Jan 12, 2020
Publications:
PubMed (5)
PubMed: 7887414924245615651432353841815381368
Other databases
https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/cf887752-8539-4177-a74d-dc5c8f8a36ed
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)
Likely pathogenic
(Nov 20, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin: germline
University of Washington Department of Laboratory Medicine,University of Washington
Accession: SCV000266133.1
First in ClinVar: Mar 20, 2016
Last updated: Mar 20, 2016
Number of individuals with the variant: 1
Pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Affected status: unknown
Allele origin: unknown
Mendelics
Accession: SCV000839112.1
First in ClinVar: Oct 10, 2018
Last updated: Oct 10, 2018
Pathogenic
(Oct 31, 2018)
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
Affected status: unknown
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894154.1
First in ClinVar: Mar 31, 2019
Last updated: Mar 31, 2019
Publications:
PubMed (1)
PubMed: 25741868
Pathogenic
(Jan 01, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin: germline
GeneKor MSA
Accession: SCV000821785.2
First in ClinVar: Oct 10, 2018
Last updated: May 04, 2020
Comment:
This sequence change replaces Arginine with Glutamine at codon 248 of the TP53 protein. The arginine residue is highly conserved among species and is located … (more)
Pathogenic
(Sep 20, 2019)
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: SCV001363225.1
First in ClinVar: Jun 22, 2020
Last updated: Jun 22, 2020
Publications:
PubMed (24)
Comment:
Variant summary: TP53 c.743G>A (p.Arg248Gln) results in a conservative amino acid change located in the p53, DNA-binding domain (IPR011615) of the encoded protein sequence. Four … (more)
Pathogenic
(Sep 07, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Ambry Genetics
Accession: SCV000185472.7
First in ClinVar: Aug 06, 2014
Last updated: May 04, 2020
Publications:
PubMed (4)
PubMed: 26822237276831802947878029489754
Comment:
​<span style="background-color:initial">The p.R248Q (also known as c.743G>A) pathogenic mutation is located in coding exon 6 of the TP53 gene. <span style="background-color:initial">This alteration results from a … (more)
Number of individuals with the variant: 1
Likely pathogenic
(Jun 25, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: yes
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001449921.1
First in ClinVar: Dec 12, 2020
Last updated: Dec 12, 2020
Number of individuals with the variant: 1
Pathogenic
(-)
criteria provided, single submitter
Method: case-control
Familial cancer of breast
Affected status: yes
Allele origin: somatic
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450492.1
First in ClinVar: Dec 12, 2020
Last updated: Dec 12, 2020
Publications:
PubMed (2)
PubMed: 3081647832000721
Number of individuals with the variant: 3
Age: 40-78 years
Sex: female
Geographic origin: Sri Lanka
Pathogenic
(Dec 03, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000149645.15
First in ClinVar: May 17, 2014
Last updated: Dec 12, 2021
Comment:
Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression and apoptotic activities, dominant-negative effect (Lomax et al., 1998; Kato et al., … (more)
Pathogenic
(Apr 05, 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: SCV000686766.2
First in ClinVar: Feb 19, 2018
Last updated: Jan 08, 2022
Comment:
This missense variant replaces arginine with glutamine at codon 248 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Pathogenic
(Dec 07, 2021)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV000253851.10
First in ClinVar: Oct 11, 2015
Last updated: May 16, 2022
Publications:
PubMed (12)
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 248 of the TP53 protein (p.Arg248Gln). … (more)
Pathogenic
(Feb 17, 2022)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV002525970.1
First in ClinVar: Jun 18, 2022
Last updated: Jun 18, 2022
Likely pathogenic
(Jul 27, 2017)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: unknown
Counsyl
Accession: SCV000785422.2
First in ClinVar: Oct 19, 2014
Last updated: Oct 19, 2014
Publications:
PubMed (4)
PubMed: 1282660917606709924245621343334
Pathogenic
(Jun 09, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Eurofins NTD LLC (GA)
Accession: SCV000232078.5
First in ClinVar: Jun 28, 2015
Last updated: Dec 15, 2018
Publications:
PubMed (1)
PubMed: 1565143
Other databases
http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TP53
http://p53.iarc.fr/ http://p53.iarc.fr/
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Sex: mixed
Pathogenic
(Nov 21, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134877.3
First in ClinVar: Jan 05, 2020
Last updated: Jan 03, 2022
Publications:
PubMed (14)
Comment:
The best available variant frequency is uninformative because it is below the disease allele frequency. Statistically enriched in patients compared to ethnically matched controls. Found … (more)
Pathogenic
(May 15, 2000)
no assertion criteria provided
Method: literature only
LI-FRAUMENI SYNDROME 1
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033397.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (3)
PubMed: 1683921156514310797439
Comment on evidence:
In 2 of 8 families with Li-Fraumeni syndrome-1 (151623), Santibanez-Koref et al. (1991) identified mutations in the TP53 gene. One was the previously described arg248-to-trp … (more)
Pathogenic
(Jul 24, 2014)
no assertion criteria provided
Method: clinical testing
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin: germline
Pathway Genomics
Accession: SCV000190000.1
First in ClinVar: Oct 19, 2014
Last updated: Oct 19, 2014
Publications:
PubMed (5)
Pathogenic
(Jun 01, 2014)
no assertion criteria provided
Method: research
Sarcoma
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin: germline
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190659.1
First in ClinVar: Dec 06, 2014
Last updated: Dec 06, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
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: SCV000504693.1
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.743G>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: SCV000504694.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (2)
PubMed: 2515796824651012
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.743G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Myelodysplastic syndrome
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504698.1
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.743G>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: SCV000504695.1
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.743G>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: SCV000504696.1
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.743G>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: SCV000504697.1
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.743G>A
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Squamous cell carcinoma of the skin
(Somatic mutation)
Affected status: yes
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504700.1
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.743G>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: SCV000504699.1
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.743G>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: SCV000504704.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (3)
PubMed: 150047242661901125157968
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.743G>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: SCV000504706.1
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.743G>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: SCV000504705.1
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.743G>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: SCV000504701.1
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.743G>A
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: SCV000504702.1
First in ClinVar: Mar 08, 2017
Last updated: Mar 08, 2017
Publications:
PubMed (4)
PubMed: 26619011246413752438122524487413
Other databases
http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000269305:c.743G>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: SCV000504703.1
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.743G>A
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: SCV000504707.1
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.743G>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: SCV000504708.1
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.743G>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: SCV000504709.1
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.743G>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: SCV000504710.1
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.743G>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: SCV000504712.1
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.743G>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: SCV000504711.1
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.743G>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: SCV000504713.1
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.743G>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: SCV000504714.1
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.743G>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: SCV000504716.1
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.743G>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: SCV000504715.1
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.743G>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: SCV000504718.1
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.743G>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: SCV000504717.1
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.743G>A
Pathogenic
(Dec 27, 2012)
no assertion criteria provided
Method: research
Li-Fraumeni syndrome 1
GERMLINE
(Autosomal dominant inheritance)
Affected status: yes
Allele origin: maternal
Donald Williams Parsons Laboratory,Baylor College of Medicine
Additional submitter:
Donald Williams Parsons Laboratory,Baylor College of Medicine
Study: CSER-BASIC3
Accession: SCV000599966.1
First in ClinVar: Oct 19, 2014
Last updated: Oct 19, 2014
Publications:
PubMed (5)
PubMed: 268222371565143213053192155213521601526
Comment:
This variant has been previously reported as disease-causing and was found once in our study maternally inherited in a 2-year-old female with neuroblastoma, in a … (more)
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Family history: yes
Age: 0-9 years
Sex: female
Ethnicity/Population group: Causasians
Pathogenic
(Apr 12, 2016)
no assertion criteria provided
Method: research
Malignant Colorectal Neoplasm
Affected status: yes
Allele origin: somatic
Genome Sciences Centre, British Columbia Cancer Agency
Study: Personalized OncoGenomics
Accession: SCV000693734.1
First in ClinVar: Mar 17, 2018
Last updated: Mar 17, 2018
Number of individuals with the variant: 1
Sex: female
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: SCV000923912.1
First in ClinVar: Jun 17, 2019
Last updated: Jun 17, 2019
Pathogenic
(Apr 30, 2019)
no assertion criteria provided
Method: research
Lip and oral cavity carcinoma
Affected status: yes
Allele origin: somatic
Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432236.1
First in ClinVar: Sep 19, 2020
Last updated: Sep 19, 2020
Publications:
PubMed (1)
PubMed: 31775759
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: SCV001434345.1
First in ClinVar: Oct 03, 2020
Last updated: Oct 03, 2020
Publications:
PubMed (1)
PubMed: 33372952
Pathogenic
(Mar 19, 2021)
no assertion criteria provided
Method: clinical testing
Ductal carcinoma in situ
Affected status: yes
Allele origin: de novo
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738480.1
First in ClinVar: Jun 26, 2021
Last updated: Jun 26, 2021
Comment:
Variant observed at low frequency
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: SCV001738502.1
First in ClinVar: Jun 26, 2021
Last updated: Jun 26, 2021
Secondary finding: yes
Pathogenic
(Aug 08, 2021)
no assertion criteria provided
Method: clinical testing
Breast carcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin: germline
Medical Genetics Laboratory, Umraniye Training and Research Hospital,University of Health Sciences
Accession: SCV001774820.1
First in ClinVar: Aug 14, 2021
Last updated: Aug 14, 2021
Indication for testing: breast cancer
Zygosity: 1 Single Heterozygote
Age: 30-39 years
Sex: female
Comment on evidence:
Invasive ductal carcinoma EST receptor - PRO receptor - HER2 receptor -
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Affected status: unknown
Allele origin: unknown
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV000692073.1
First in ClinVar: Feb 19, 2018
Last updated: Feb 19, 2018
Likely pathogenic
(Jul 25, 2019)
no assertion criteria provided
Method: clinical testing
Lymphoma
Affected status: yes
Allele origin: somatic
Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center
Accession: SCV000930032.1
First in ClinVar: Aug 04, 2019
Last updated: Aug 04, 2019
Likely pathogenic
(Aug 31, 2019)
no assertion criteria provided
Method: clinical testing
Multiple myeloma
Affected status: yes
Allele origin: somatic
Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center
Accession: SCV001132099.1
First in ClinVar: Dec 23, 2019
Last updated: Dec 23, 2019

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
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
Pattern of nucleotide variants of TP53 and their correlation with the expression of p53 and its downstream proteins in a Sri Lankan cohort of breast and colorectal cancer patients. Manoharan V BMC cancer 2020 PMID: 32000721
Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance. Batta N World journal of surgical oncology 2019 PMID: 31775759
Divergent clonal evolution of a common precursor to mantle cell lymphoma and classic Hodgkin lymphoma. Tashkandi H Cold Spring Harbor molecular case studies 2019 PMID: 31395597
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
Hematologic malignancies and Li-Fraumeni syndrome. Swaminathan M Cold Spring Harbor molecular case studies 2019 PMID: 30709875
The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. McNamara CJ Blood advances 2018 PMID: 30327374
Identification and characterization of TP53 gene Allele Dropout in Li-Fraumeni syndrome and Oral cancer cohorts. Haque MM Scientific reports 2018 PMID: 30076369
The landscape of genomic alterations across childhood cancers. Gröbner SN Nature 2018 PMID: 29489754
Inherited DNA-Repair Defects in Colorectal Cancer. AlDubayan SH American journal of human genetics 2018 PMID: 29478780
Molecular characterization of <i>ERBB2</i>-amplified colorectal cancer identifies potential mechanisms of resistance to targeted therapies: a report of two instructive cases. Owen DR Cold Spring Harbor molecular case studies 2018 PMID: 29438965
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
Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage. Zerdoumi Y Human molecular genetics 2017 PMID: 28369373
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Döhner H Blood 2017 PMID: 27895058
Somatic and Germline <i>TP53</i> Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors. Sherborne AL Clinical cancer research : an official journal of the American Association for Cancer Research 2017 PMID: 27683180
The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Stengel A Leukemia 2017 PMID: 27680515
TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Welch JS The New England journal of medicine 2016 PMID: 27959731
TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Kadia TM Cancer 2016 PMID: 27463065
Genomic Classification and Prognosis in Acute Myeloid Leukemia. Papaemmanuil E The New England journal of medicine 2016 PMID: 27276561
Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors. Parsons DW JAMA oncology 2016 PMID: 26822237
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Chang MT Nature biotechnology 2016 PMID: 26619011
Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival. Mullany LK Neoplasia (New York, N.Y.) 2015 PMID: 26585234
TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. Hou HA Blood cancer journal 2015 PMID: 26230955
TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. Ok CY Journal of hematology & oncology 2015 PMID: 25952993
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. MacConaill LE The Journal of molecular diagnostics : JMD 2014 PMID: 25157968
A pathogenic mosaic TP53 mutation in two germ layers detected by next generation sequencing. Behjati S PloS one 2014 PMID: 24810334
Mutant p53 in cancer: new functions and therapeutic opportunities. Muller PA Cancer cell 2014 PMID: 24651012
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
Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Rossi D Blood 2014 PMID: 24501221
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
Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis. Hanel W Cell death and differentiation 2013 PMID: 23538418
Functional characterisation of p53 mutants identified in breast cancers with suboptimal responses to anthracyclines or mitomycin. Berge EO Biochimica et biophysica acta 2013 PMID: 23246812
The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis. Leroy B Nucleic acids research 2013 PMID: 23161690
A novel hierarchical prognostic model of AML solely based on molecular mutations. Grossmann V Blood 2012 PMID: 22915647
TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Rücker FG Blood 2012 PMID: 22186996
Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Melhem-Bertrandt A Cancer 2012 PMID: 21761402
Effects of temperature on the p53-DNA binding interactions and their dynamical behavior: comparing the wild type to the R248Q mutant. Barakat K PloS one 2011 PMID: 22110706
Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Villani A The Lancet. Oncology 2011 PMID: 21601526
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
TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. Jädersten M Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 PMID: 21519010
Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Monti P Molecular cancer research : MCR 2011 PMID: 21343334
Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li-Fraumeni syndrome. Wu CC Human genetics 2011 PMID: 21305319
Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung cancer NCI-H1299 cells. Yoshikawa K Biomedical research (Tokyo, Japan) 2010 PMID: 21187651
Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation. Jordan JJ Molecular cancer research : MCR 2010 PMID: 20407015
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
Mutants of the tumour suppressor p53 L1 loop as second-site suppressors for restoring DNA binding to oncogenic p53 mutations: structural and biochemical insights. Merabet A The Biochemical journal 2010 PMID: 20113312
High frequency of de novo mutations in Li-Fraumeni syndrome. Gonzalez KD Journal of medical genetics 2009 PMID: 19556618
Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. Bougeard G Journal of medical genetics 2008 PMID: 18511570
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
Functional analysis and molecular modeling show a preserved wild-type activity of p53(C238Y). Ferrone M Molecular cancer therapeutics 2006 PMID: 16818505
Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB. Benoit V Oncogene 2006 PMID: 16682957
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
Mutant p53 proteins bind DNA in a DNA structure-selective mode. Göhler T Nucleic acids research 2005 PMID: 15722483
Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. Bendig I Cancer genetics and cytogenetics 2004 PMID: 15381368
Mutant p53 expression enhances drug resistance in a hepatocellular carcinoma cell line. Chan KT Cancer chemotherapy and pharmacology 2004 PMID: 15004724
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
A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants. Friedler A Proceedings of the National Academy of Sciences of the United States of America 2002 PMID: 11782540
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Vahteristo P Cancer research 2001 PMID: 11479205
Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites. Rapakko K British journal of cancer 2001 PMID: 11139324
Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. Tachibana I American journal of medical genetics 2000 PMID: 10797439
Hot-spot mutants of p53 core domain evince characteristic local structural changes. Wong KB Proceedings of the National Academy of Sciences of the United States of America 1999 PMID: 10411893
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
Identification of human p53 mutations with differential effects on the bax and p21 promoters using functional assays in yeast. Flaman JM Oncogene 1998 PMID: 9546439
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Varley JM Cancer research 1997 PMID: 9242456
Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Frebourg T American journal of human genetics 1995 PMID: 7887414
Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. Ory K The EMBO journal 1994 PMID: 8062826
Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. Toguchida J The New England journal of medicine 1992 PMID: 1565143
p53 germline mutations in Li-Fraumeni syndrome. Santibáñez-Koref MF Lancet (London, England) 1991 PMID: 1683921
http://docm.genome.wustl.edu/variants/ENST00000269305:c.743G>A - - - -
http://p53.iarc.fr/ - - - -
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TP53 - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/cf887752-8539-4177-a74d-dc5c8f8a36ed - - - -

Text-mined citations for rs11540652...

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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 Oct 01, 2022