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, 19468865, 20522432) and is extremely rare in general population databases. Experimental studies have shown that this missense change affects TP53 protein function (PMID 8080050, 10871862, 17606709,17311302, 21343334). This variant is located within a mutational hotspot that encodes the DNA-binding domain of the p53 protein. Arg213 is a highly conserved residue and multiple lines of algorithms predict deleterious effect of the p.Arg213Gln change. Therefore, we classify this c.638G>A (p.Arg213Gln) variant as pathogenic.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 43
- First in ClinVar:
- Jun 9, 2014
- Most recent Submission:
- May 20, 2023
- Last evaluated:
- Apr 19, 2023
- Accession:
- VCV000135359.49
- Variation ID:
- 135359
- Description:
- single nucleotide variant
Help
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
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000546.6:c.638G>A MANE Select NP_000537.3:p.Arg213Gln missense NM_001126112.3:c.638G>A NP_001119584.1:p.Arg213Gln missense NM_001126113.3:c.638G>A NP_001119585.1:p.Arg213Gln missense NM_001126114.3:c.638G>A NP_001119586.1:p.Arg213Gln missense NM_001126115.2:c.242G>A NP_001119587.1:p.Arg81Gln missense NM_001126116.2:c.242G>A NP_001119588.1:p.Arg81Gln missense NM_001126117.2:c.242G>A NP_001119589.1:p.Arg81Gln missense NM_001126118.2:c.521G>A NP_001119590.1:p.Arg174Gln missense NM_001276695.3:c.521G>A NP_001263624.1:p.Arg174Gln missense NM_001276696.3:c.521G>A NP_001263625.1:p.Arg174Gln missense NM_001276697.3:c.161G>A NP_001263626.1:p.Arg54Gln missense NM_001276698.3:c.161G>A NP_001263627.1:p.Arg54Gln missense NM_001276699.3:c.161G>A NP_001263628.1:p.Arg54Gln missense NM_001276760.3:c.521G>A NP_001263689.1:p.Arg174Gln missense NM_001276761.3:c.521G>A NP_001263690.1:p.Arg174Gln missense NC_000017.11:g.7674893C>T NC_000017.10:g.7578211C>T NG_017013.2:g.17658G>A LRG_321:g.17658G>A LRG_321t1:c.638G>A LRG_321p1:p.Arg213Gln P04637:p.Arg213Gln - 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
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 5 | criteria provided, multiple submitters, no conflicts | Nov 16, 2021 | RCV000420734.11 | |
| Pathogenic | 4 | criteria provided, multiple submitters, no conflicts | Jan 30, 2023 | RCV000123099.20 | |
| Pathogenic | 4 | criteria provided, multiple submitters, no conflicts | Apr 19, 2023 | RCV000144664.6 | |
| Pathogenic | 4 | criteria provided, multiple submitters, no conflicts | Jun 18, 2022 | RCV000130072.11 | |
| Pathogenic | 1 | criteria provided, single submitter | Aug 9, 2019 | RCV001798386.3 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000425846.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000427005.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000419636.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000430601.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000420908.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000422008.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000428223.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000432438.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000430946.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000432016.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000438230.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000438582.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000420459.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000437236.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000420595.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000436981.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444077.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424188.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000443346.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444201.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000430755.2 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000441015.2 | |
| drug response | 1 | no assertion criteria provided | Nov 27, 2017 | RCV000626448.2 | |
| Pathogenic | 1 | no assertion criteria provided | Apr 30, 2019 | RCV001255672.2 | |
| not provided | 1 | no assertion provided | Sep 19, 2013 | RCV000122176.2 |
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 |
2836 | 2931 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Feb 21, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434920.1
First in ClinVar: Oct 02, 2020 Last updated: Oct 02, 2020 |
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)
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, 19468865, 20522432) and is extremely rare in general population databases. Experimental studies have shown that this missense change affects TP53 protein function (PMID 8080050, 10871862, 17606709,17311302, 21343334). This variant is located within a mutational hotspot that encodes the DNA-binding domain of the p53 protein. Arg213 is a highly conserved residue and multiple lines of algorithms predict deleterious effect of the p.Arg213Gln change. Therefore, we classify this c.638G>A (p.Arg213Gln) variant as pathogenic. (less)
|
|
|
Pathogenic
(Jan 13, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469324.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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)
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 for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Two other pathogenic or likely pathogenic variants affect the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function. Inconclusive segregation with disease (less)
|
|
|
Pathogenic
(Oct 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000166400.11
First in ClinVar: Jun 15, 2014 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 213 of the TP53 protein (p.Arg213Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 213 of the TP53 protein (p.Arg213Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Li-Fraumeni syndrome (LFS) or LFS-associated malignancies (PMID: 16494995, 16736287, 17541742, 18208484, 19468865, 20522432, 23259501). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 135359). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 16736287, 17606709, 21343334). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 30, 2023)
|
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: SCV003800820.1
First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023 |
Comment:
Variant summary: TP53 c.638G>A (p.Arg213Gln) results in a conservative amino acid change located in the p53, DNA-binding domain (IPR011615) of the encoded protein sequence. Four … (more)
Variant summary: TP53 c.638G>A (p.Arg213Gln) results in a conservative amino acid change located in the p53, DNA-binding domain (IPR011615) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251462 control chromosomes (gnomAD). c.638G>A has been reported in the literature in multiple individuals affected with Li-Fraumeni Syndrome and associated cancers, and has been shown to segregate with disease within families (e.g. Ruijs_2006, Arcand_2008, Sheng_2020). These data indicate that the variant is very likely to be associated with disease. Experimental studies have shown that this missense change significantly affects the functional activity of the TP53 protein, diminishing its DNA-binding and transcriptional transactivation activities in yeast-based assays, and has been functionally classified as a partial deficiency (PD) or severe deficiency (SD) allele (PMID: 16736287, 21343334, 12826609, 17606709). Ten ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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|
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Pathogenic
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517027.7
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
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)
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 of the p21 gene, resulting in an inability to up-regulate cell cycle arrest and apoptosis (Pan 2000, Kato 2003, Monti 2011, Zhang 2014, Kotler 2018); Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25268584, 16494995, 29979965, 28472496, 30224644, 28643165, 29058986, 25925845, 10871862, 14583457, 23259501, 16736287, 19468865, 8080050, 24728327, 1915267, 8492087, 21343334, 17606709, 24384472, 26270727, 26829319, 20522432, 28369373, 29076966, 18208484, 28861920, 29489754, 28724667, 30455982, 30675318, 30299350, 30720243, 30840781, 31119730, 30577483, 31481248, 31105275, 31447099, 33138793, 33818021, 17541742, 15510160) (less)
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|
|
Pathogenic
(Oct 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV003843119.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
The TP53 c.638G>A (p.Arg213Gln) missense change has a maximum subpopulation frequency of 0.0046% in gnomAD v2.1.1 (http://gnomad.broadinstitute.org). This variant has been reported in multiple individuals … (more)
The TP53 c.638G>A (p.Arg213Gln) missense change has a maximum subpopulation frequency of 0.0046% in gnomAD v2.1.1 (http://gnomad.broadinstitute.org). This variant has been reported in multiple individuals with Li-Fraumeni syndrome (LFS) or LFS-associated cancers and has been found to segregate with disease in families (PMID: 16494995, 16736287, 17541742, 18208484, 19468865, 20522432, 25293557, 28369373). Computational evidence supports a deleterious effect of this variant on protein function (Align GVGD = C35, BayesDel = 0.5033). Transactivation assays show a low functioning allele according to Kato et al., and evidence of loss of function and a dominant negative effect according to Giacomelli et al. (PMID 12826609, 30224644). This variant is a somatic hotspot variant in tumors according to the Cancer Hotspots database (cancerhotspots.org). In summary, this variant meets criteria to be classified as pathogenic. (less)
|
|
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Pathogenic
(Jan 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000731632.3
First in ClinVar: Apr 09, 2018 Last updated: Jul 03, 2020 |
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Mar 27, 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: SCV001449717.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Oct 30, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292157.2
First in ClinVar: Jul 08, 2016 Last updated: Mar 25, 2020 |
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)
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 may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant results in the loss of DNA binding and transactivation activity of TP53 protein (PMID: 7885831, 10871862, 12826609, 16736287, 24384472). This variant has been reported in an individual affected with Li-Fraumeni syndrome (Color internal data) and in individuals meeting the Chompret criteria of Li-Fraumeni syndrome (PMID: 17541742, 23259501). In a large pedigree that meets the Birch criteria of Li-Fraumeni-like syndrome, this variant has been shown to segregate with late-onset breast cancer, ovarian cancer, colorectal cancer, renal cell cancer, melanoma, mesothelioma and lung cancer in 12 family members (PMID: 16736287). This variant has been observed in individuals not meeting Li-Fraumeni syndrome diagnostic criteria but affected with breast cancer (PMID: 17541742, 20522432, 31119730, 32019277; Color internal data) and sarcoma (PMID: 19468865). An analysis of IARC's TP53 germline variant dataset has shown this variant to exhibit reduced penetrance (PMID: 29076966). This variant has been identified in 1/251462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. This variant may display reduced penetrance relative to typical pathogenic TP53 variants. Medical management should be considered based on the individual’s personal and family history. (less)
|
|
|
Pathogenic
(Aug 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV002042828.1
First in ClinVar: Jan 01, 2022 Last updated: Jan 01, 2022 |
|
|
|
Pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002582482.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
|
Pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002583142.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
|
Pathogenic
(Nov 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184899.8
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
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)
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 nucleotide position 638. The arginine at codon 213 is replaced by glutamine, an amino acid with similar properties. In one study, p.R213Q was detected in a 3-month-old boy with choroid plexus carcinoma whose unaffected father was also found to carry the alteration (Becherini et al. Neuropathol. Appl. Neurobiol. 2008 Oct;34(5):564-8). Other studies have reported this alteration in individuals with clinical histories suspicious for Li-Fraumeni syndrome (LFS) (Achatz MI et al. Cancer Lett. 2007 Jan 8;245(1-2):96-102; Arcand SL et al. Breast Cancer Res Treat. 2008 Apr;108(3):399-408; Pinto C et al. Fam. Cancer. 2009 May;8(4):383-90; Ruijs MW et al. J. Med. Genet. 2010 Jun;47(6):421-8; Desmond A et al. JAMA Oncol. 2015 Oct;1(7):943-51). This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9; Zerdoumi Y et al. Hum. Mol. Genet., 2017 07;26:2591-2602). Studies conducted in human cell lines are equivocal about this variant's ability to suppress cell growth (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration has been detected in multiple families satisfying clinical diagnostic criteria for LFS to date (Ambry internal data). However, it has also been detected in individuals with atypical/mild LFS phenotypes, suggesting variable expressivity and penetrance (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as a pathogenic mutation. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Apr 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV003925607.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
_x000D_ Criteria applied: PS3, PS4, PM5_STR, PM2_SUP
|
|
|
drug response
(Nov 27, 2017)
|
no assertion criteria provided
Method: clinical testing
|
PARP Inhibitor response
Drug used for
Cancer
Affected status: yes
Allele origin:
somatic
|
Oxford Haemato-Oncology Service,Oxford University Hospitals NHS Foundation Trust
Accession: SCV000734838.1
First in ClinVar: May 06, 2018 Last updated: May 06, 2018 |
Method: PCR-Free library Preparation on germline and tumour. Data analyzed after Tumour-Normal Substraction.
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
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 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
|
Pathogenic
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189995.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
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: SCV000509198.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509199.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509201.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509196.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509197.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509200.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509203.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509202.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
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: SCV000509204.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Uterine carcinosarcoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509205.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Adenoid cystic carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509207.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Renal cell carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509208.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Breast neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509209.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Nasopharyngeal neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509206.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Ovarian serous cystadenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509211.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Transitional cell carcinoma of the bladder
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509212.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509216.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Malignant melanoma of skin
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509217.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Squamous cell carcinoma of the skin
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509213.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509210.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Neoplasm of brain
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509215.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(May 31, 2016)
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no assertion criteria provided
Method: literature only
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Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000509214.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Apr 30, 2019)
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no assertion criteria provided
Method: research
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Lip and oral cavity carcinoma
Affected status: yes
Allele origin:
somatic
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Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432237.1
First in ClinVar: Sep 18, 2020 Last updated: Sep 18, 2020 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953963.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Aug 26, 2022)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV002589031.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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not provided
(Sep 19, 2013)
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no assertion provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000086391.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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Functional evidence
Help| 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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer. | Sheng S | International journal of cancer | 2020 | PMID: 31119730 |
| 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 |
| The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. | McNamara CJ | Blood advances | 2018 | PMID: 30327374 |
| 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 |
| Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | Döhner H | Blood | 2017 | PMID: 27895058 |
| 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 |
| 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 |
| Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. | Desmond A | JAMA oncology | 2015 | PMID: 26270727 |
| 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 |
| 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 |
| 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 |
| Number of rare germline CNVs and TP53 mutation types. | Silva AG | Orphanet journal of rare diseases | 2012 | PMID: 23259501 |
| 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 |
| Pleomorphic carcinoma of the lung arising in a patient with Li-Fraumeni syndrome: report of a case. | Kato T | Surgery today | 2011 | PMID: 21626334 |
| 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 |
| 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 |
| Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation. | Jordan JJ | Molecular cancer research : MCR | 2010 | PMID: 20407015 |
| 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 |
| Functional analysis and molecular modeling show a preserved wild-type activity of p53(C238Y). | Ferrone M | Molecular cancer therapeutics | 2006 | PMID: 16818505 |
| 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 |
| 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 |
| 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...
HelpThese 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 May 27, 2023