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NM_000546.6(TP53):c.638G>A (p.Arg213Gln)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
36 (Most recent: Nov 24, 2021)
Last evaluated:
Nov 16, 2021
Accession:
VCV000135359.17
Variation ID:
135359
Description:
single nucleotide variant
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NM_000546.6(TP53):c.638G>A (p.Arg213Gln)

Allele ID
139098
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7674893 (GRCh38) GRCh38 UCSC
17: 7578211 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P04637:p.Arg213Gln
LRG_321:g.17658G>A
LRG_321t1:c.638G>A LRG_321p1:p.Arg213Gln
... more HGVS
Protein change
R174Q, R213Q, R81Q, R54Q
Other names
-
Canonical SPDI
NC_000017.11:7674892:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA000302
UniProtKB: P04637#VAR_005955
dbSNP: rs587778720
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 29, 2020 RCV000123099.12
Pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 30, 2020 RCV000130072.6
Pathogenic 5 criteria provided, multiple submitters, no conflicts Nov 16, 2021 RCV000420734.8
Pathogenic 1 no assertion criteria provided Jul 24, 2014 RCV000144664.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000419636.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000420908.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000422008.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000432438.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000437236.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000444077.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000428223.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000420459.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000420595.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000425846.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000424188.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000427005.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000430946.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000430601.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000432016.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000430755.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000436981.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000438230.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000438582.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000441015.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000443346.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000444201.1
drug response 1 no assertion criteria provided Nov 27, 2017 RCV000626448.1
Pathogenic 1 no assertion criteria provided Apr 30, 2019 RCV001255672.1
not provided 1 no assertion provided Sep 19, 2013 RCV000122176.1
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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
2215 2278

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 30, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184899.7
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (7)
Comment:
The p.R213Q pathogenic mutation (also known as c.638G>A), located in coding exon 5 of the TP53 gene, results from a G to A substitution at … (more)
Pathogenic
(Oct 29, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV000166400.9
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (11)
Comment:
This sequence change replaces arginine with glutamine at codon 213 of the TP53 protein (p.Arg213Gln). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Jan 10, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000731632.3
Submitted: (Jun 03, 2020)
Evidence details
Publications
PubMed (8)
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Pathogenic
(Feb 21, 2019)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434920.1
Submitted: (Apr 23, 2020)
Evidence details
Comment:
The c.638G>A (p.Arg213Gln) variant in the TP53 gene has been reported in multiple families affected with Li-Fraumeni (LFS) or Li-Fraumeni-like (LFL) syndromes (PMID 16736287, 16494995, … (more)
Pathogenic
(Mar 27, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001449717.1
Submitted: (Nov 26, 2020)
Evidence details
Pathogenic
(Jan 13, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469324.1
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (6)
Comment:
The best available variant frequency is uninformative because there are too few occurrences in population data. Found in at least one patient with expected phenotype … (more)
Pathogenic
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000292157.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces arginine with glutamine at codon 213 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant … (more)
Pathogenic
(Nov 16, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000517027.6
Submitted: (Nov 24, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect: partial to non-functional transactivation activity, deficient in targeting the consensus binding sequencing of p53 in the regulatory region … (more)
Pathogenic
(Jul 24, 2014)
no assertion criteria provided
Method: clinical testing
Li-Fraumeni syndrome 1
Allele origin: germline
Pathway Genomics
Accession: SCV000189995.1
Submitted: (Aug 08, 2014)
Evidence details
Publications
PubMed (3)
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
None
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509196.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neoplasm of the large intestine
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509197.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Adrenocortical carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509198.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Carcinoma of esophagus
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509199.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Adenocarcinoma of prostate
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509200.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Pancreatic adenocarcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509201.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Hepatocellular carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509202.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
None
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509203.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Squamous cell lung carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509204.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Uterine Carcinosarcoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509205.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Nasopharyngeal Neoplasms
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509206.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Adenoid cystic carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509207.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Renal cell carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509208.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Breast neoplasm
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509209.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Malignant neoplasm of body of uterus
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509210.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Ovarian Serous Cystadenocarcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509211.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Transitional cell carcinoma of the bladder
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509212.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Squamous cell carcinoma of the skin
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509213.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Adenocarcinoma of stomach
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509214.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neoplasm of brain
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509215.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Glioblastoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509216.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Malignant melanoma of skin
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000509217.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
drug response
(Nov 27, 2017)
no assertion criteria provided
Method: clinical testing
PARP Inhibitor response
Drug used for Cancer
Allele origin: somatic
Oxford Haemato-Oncology Service,Oxford University Hospitals NHS Foundation Trust
Accession: SCV000734838.1
Submitted: (Feb 05, 2018)
Evidence details
Pathogenic
(Apr 30, 2019)
no assertion criteria provided
Method: research
Lip and oral cavity carcinoma
Allele origin: somatic
Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432237.1
Submitted: (Feb 01, 2020)
Evidence details
Publications
PubMed (1)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905965.1
Submitted: (Sep 20, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953963.1
Submitted: (Sep 30, 2021)
Evidence details
not provided
(Sep 19, 2013)
no assertion provided
Method: reference population
AllHighlyPenetrant
Allele origin: germline
ITMI
Accession: SCV000086391.1
Submitted: (May 29, 2014)
Comment:
Please see associated publication for description of ethnicities
Evidence details
Publications
PubMed (1)

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
Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance. Batta N World journal of surgical oncology 2019 PMID: 31775759
High prevalence of cancer-associated TP53 variants in the gnomAD database: A word of caution concerning the use of variant filtering. Soussi T Human mutation 2019 PMID: 30720243
Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in TP53. Gatineau-Sailliant S Journal of pediatric hematology/oncology 2019 PMID: 30299350
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
Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history. de Andrade KC Human mutation 2017 PMID: 28861920
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
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Chang MT Nature biotechnology 2016 PMID: 26619011
Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. Desmond A JAMA oncology 2015 PMID: 26270727
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. Bodian DL PloS one 2014 PMID: 24728327
The impact of R213 mutation on p53-mediated p21 activity. Zhang Y Biochimie 2014 PMID: 24384472
Number of rare germline CNVs and TP53 mutation types. Silva AG Orphanet journal of rare diseases 2012 PMID: 23259501
Pleomorphic carcinoma of the lung arising in a patient with Li-Fraumeni syndrome: report of a case. Kato T Surgery today 2011 PMID: 21626334
Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Monti P Molecular cancer research : MCR 2011 PMID: 21343334
TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. Ruijs MW Journal of medical genetics 2010 PMID: 20522432
TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset. Pinto C Familial cancer 2009 PMID: 19468865
Choroid plexus carcinoma: a new case associated with a novel TP53 germ line mutation. Becherini F Neuropathology and applied neurobiology 2008 PMID: 18208484
Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families. Arcand SL Breast cancer research and treatment 2008 PMID: 17541742
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
The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families. Achatz MI Cancer letters 2007 PMID: 16494995
Late-onset common cancers in a kindred with an Arg213Gln TP53 germline mutation. Ruijs MW Familial cancer 2006 PMID: 16736287
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
Clinical significance of p53 mutations in newly diagnosed Burkitt's lymphoma and acute lymphoblastic leukemia: a report of 48 cases. Preudhomme C Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1995 PMID: 7707106
Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness. Hsiao M The American journal of pathology 1994 PMID: 8080050
http://docm.genome.wustl.edu/variants/ENST00000269305:c.638G>A - - - -

Text-mined citations for rs587778720...

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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 Dec 04, 2021