The p.Arg175His variant in TP53 has been reported in >16 individuals with Li-Fra umeni syndrome, and segregated with disease in 3 affected relatives from 1 famil y (McIntyre 1994, Varley 1997, Wong 2006, Bougeard 2008, Walsh 2011, Melhem-Bert randt 2012, Park 2016). This variant has also been reported by another clinical laboratory in ClinVar (Variation ID# 12374). In vitro functional studies provide some evidence that the p.Arg175His variant may impact protein function (Kogan-S akin 2011, Grugan 2013) and an in-vivo mouse model has shown that this variant c auses TP53-related tumors (Liu 2010). Additionally, the p.Arg175His variant has been identified in 1/111550 European chromosomes by gnomAD (http://gnomad.broadi nstitute.org). Computational prediction tools and conservation analysis suggest that the p.Arg175His variant may impact the protein and 3 other amino acid chang es at this position (Leu, Gly, Cys) have been associated with Li-Fraumeni syndro me (HGMD database; Stenson 2017). In summary, this variant meets criteria to be classified as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manne r based on segregation studies, increased prevalence in affected individuals, ve ry low frequency in controls and functional evidence. ACMG/AMP Criteria applied: PS4, PP1, PS3, PM2.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 24 (Most recent: Sep 30, 2021)
- Last evaluated:
- Jan 4, 2021
- Accession:
- VCV000012374.21
- Variation ID:
- 12374
- Description:
- single nucleotide variant
Help
NM_000546.6(TP53):c.524G>A (p.Arg175His)
- Allele ID
- 27413
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17p13.1
- Genomic location
- 17: 7675088 (GRCh38) GRCh38 UCSC
- 17: 7578406 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceP04637:p.Arg175His LRG_321:g.17463G>A LRG_321t1:c.524G>A LRG_321p1:p.Arg175His LRG_321t2:c.524G>A LRG_321:p.Arg175His LRG_321t4:c.524G>A LRG_321p4:p.Arg175His LRG_321t3:c.524G>A LRG_321p3:p.Arg175His LRG_321t5:c.128G>A LRG_321p5:p.Arg43His LRG_321t6:c.128G>A LRG_321p6:p.Arg43His LRG_321t7:c.128G>A LRG_321p7:p.Arg43His LRG_321t8:c.407G>A LRG_321p8:p.Arg136His NM_000546.5:c.524G>A NP_000537.3:p.Arg175His missense NC_000017.10:g.7578406C>T NC_000017.11:g.7675088C>T NG_017013.2:g.17463G>A NM_000546.6:c.524G>A MANE Select NP_000537.3:p.Arg175His missense NM_001126112.2:c.524G>A NP_001119584.1:p.Arg175His missense NM_001126113.2:c.524G>A NP_001119585.1:p.Arg175His missense NM_001126114.2:c.524G>A NP_001119586.1:p.Arg175His missense NM_001126115.1:c.128G>A NP_001119587.1:p.Arg43His missense NM_001126116.1:c.128G>A NP_001119588.1:p.Arg43His missense NM_001126117.1:c.128G>A NP_001119589.1:p.Arg43His missense NM_001126118.1:c.407G>A NP_001119590.1:p.Arg136His missense NM_001276695.2:c.407G>A NP_001263624.1:p.Arg136His missense NM_001276696.2:c.407G>A NP_001263625.1:p.Arg136His missense NM_001276697.2:c.47G>A NP_001263626.1:p.Arg16His missense NM_001276698.2:c.47G>A NP_001263627.1:p.Arg16His missense NM_001276699.2:c.47G>A NP_001263628.1:p.Arg16His missense NM_001276760.2:c.407G>A NP_001263689.1:p.Arg136His missense NM_001276761.2:c.407G>A NP_001263690.1:p.Arg136His missense - Protein change
- R175H, R136H, R43H, R16H
- Other names
- p.R175H:CGC>CAC
- Canonical SPDI
- NC_000017.11:7675087:C:T
- Functional consequence
- variation affecting protein function [Variation Ontology VariO:0003]
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD), exomes 0.00000
- Exome Aggregation Consortium (ExAC) 0.00001
- Links
- ClinGen: CA000251
- UniProtKB: P04637#VAR_005932
- OMIM: 191170.0030
- dbSNP: rs28934578
- 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 | Dec 15, 2020 | RCV000013173.24 | |
| Pathogenic | 2 | criteria provided, multiple submitters, no conflicts | Sep 13, 2018 | RCV000131301.8 | |
| Pathogenic | 6 | criteria provided, multiple submitters, no conflicts | Jan 4, 2021 | RCV000213054.10 | |
| Pathogenic | 2 | criteria provided, multiple submitters, no conflicts | Oct 21, 2020 | RCV000204931.11 | |
| Pathogenic | 1 | criteria provided, single submitter | Oct 31, 2018 | RCV000763419.1 | |
| Pathogenic | 1 | criteria provided, single submitter | - | RCV001270268.1 | |
| Pathogenic | 1 | criteria provided, single submitter | - | RCV001270269.1 | |
| Pathogenic | 1 | no assertion criteria provided | Jul 29, 2016 | RCV000239398.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | Jul 14, 2015 | RCV000421746.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | Dec 1, 2018 | RCV000785352.1 | |
| Pathogenic | 1 | no assertion criteria provided | Apr 30, 2019 | RCV001255668.1 | |
| Pathogenic | 1 | no assertion criteria provided | Mar 19, 2021 | RCV001527463.1 | |
| not provided | 1 | no assertion provided | Mar 10, 2016 | RCV000428918.1 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2205 | 2268 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
Pathogenic
(Apr 17, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Allele origin:
germline
|
PreventionGenetics,PreventionGenetics
Accession: SCV000806241.1
Submitted: (Jan 29, 2018) |
|
|
Pathogenic
(Jul 24, 2017)
|
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: SCV000731790.2
Submitted: (Mar 21, 2019) |
Comment:
The p.Arg175His variant in TP53 has been reported in >16 individuals with Li-Fra umeni syndrome, and segregated with disease in 3 affected relatives from 1 … (more)
The p.Arg175His variant in TP53 has been reported in >16 individuals with Li-Fra umeni syndrome, and segregated with disease in 3 affected relatives from 1 famil y (McIntyre 1994, Varley 1997, Wong 2006, Bougeard 2008, Walsh 2011, Melhem-Bert randt 2012, Park 2016). This variant has also been reported by another clinical laboratory in ClinVar (Variation ID# 12374). In vitro functional studies provide some evidence that the p.Arg175His variant may impact protein function (Kogan-S akin 2011, Grugan 2013) and an in-vivo mouse model has shown that this variant c auses TP53-related tumors (Liu 2010). Additionally, the p.Arg175His variant has been identified in 1/111550 European chromosomes by gnomAD (http://gnomad.broadi nstitute.org). Computational prediction tools and conservation analysis suggest that the p.Arg175His variant may impact the protein and 3 other amino acid chang es at this position (Leu, Gly, Cys) have been associated with Li-Fraumeni syndro me (HGMD database; Stenson 2017). In summary, this variant meets criteria to be classified as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manne r based on segregation studies, increased prevalence in affected individuals, ve ry low frequency in controls and functional evidence. ACMG/AMP Criteria applied: PS4, PP1, PS3, PM2. (less)
|
|
Pathogenic
(Sep 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186273.7
Submitted: (Nov 30, 2020) |
Comment:
The p.R175H pathogenic mutation (also known as c.524G>A), located in coding exon 4 of the TP53 gene, results from a G to A substitution at … (more)
The p.R175H pathogenic mutation (also known as c.524G>A), located in coding exon 4 of the TP53 gene, results from a G to A substitution at nucleotide position 524. This changes the amino acid from an arginine to a histidine at codon 175. This alteration occurs at a well-characterized mutation "hotspot" in the functionally critical DNA binding domain, and is associated with a classic LFS-associated tumor spectrum, including osteosarcomas, rhabdomyosarcomas, early onset colon cancer, breast cancer, and pediatric adrenal cortical tumors (McIntyre JF et al. J. Clin. Oncol. 1994 May;12(5):925-930; Varley JM et al. J. Med. Genet. 1995 Dec;32:942-945; Wong P et al. Gastroenterology. 2006 Jan;130:73-79; Hwang SM et al. Korean J. Lab Med. 2008 Dec;28(6):493-497; Melhem-Bertrandt A et al. Cancer. 2012 Feb;118(4):908-13; Choong SS et al. Clin. Genet. 2012 Dec;82(6):564-8; Maxwell KN et al. Am. J. Hum. Genet. 2016 May;98:801-17; Park KJ et al. Ann. Lab. Med. 2016 Sep;36:463-8; Dudley B et al. Cancer. 2018 Apr;124(8):1691-1700). Functional studies have shown that this alteration leads to an increase in cell colony growth and classified it as a severe transactivation deficiency allele with less than 25% residual protein activity compared to wildtype alleles (Monti P et al. Mol. Cancer Res. 2011 Mar;9:271-279; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul 8;100(14):8424-9; Wasserman JD et al. J. Clin. Oncol. 2015 Feb;33(6):602-9; Zerdoumi Y et al. Hum. Mol. Genet. 2017 07;26(14):2812). Based on the available evidence, this alteration is classified as a pathogenic mutation. (less)
|
|
Pathogenic
(Dec 15, 2020)
|
criteria provided, single submitter
Method: research
|
Li-Fraumeni syndrome 1
Allele origin:
germline
|
Department of Pediatrics,Memorial Sloan Kettering Cancer Center
Accession: SCV001478188.1
Submitted: (Dec 16, 2020) |
|
|
Pathogenic
(Jan 04, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Allele origin:
germline
|
GeneDx
Accession: SCV000211798.12
Submitted: (Jul 20, 2021) |
Comment:
Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Kato et al., 2003; Monti et al., 2011; Wasserman et al., … (more)
Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Kato et al., 2003; Monti et al., 2011; Wasserman et al., 2015; Kotler et al., 2018); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31447099, 31105275, 15510160, 12826609, 19556618, 21343334, 25584008, 29979965, 8118819, 8164043, 10864200, 12200603, 16401470, 22233476, 28369373, 30577483, 30840781, 30093976, 29324801, 30092803, 30720243, 30709875, 28472496, 29753700, 29360550, 28975465, 29470806, 19127115, 29360161, 28818432, 29416795, 27153395, 12610779, 11494139, 11370630, 8308926, 7887414, 8099841, 23792586, 20689556, 15492269, 21426305, 22006311, 24573247, 22286061, 21305319, 17606709, 21761402, 24651015, 20128691, 24729566, 15170137, 29489754, 28861920, 28724667, 15607981, 15607980, 27516001, 27374712, 27714481, 27501770, 27323394, 23172776, 22265402, 21601526, 22851211, 21059199, 20501846, 18511570, 17308077, 16551709, 15951970) (less)
|
|
Pathogenic
(Mar 18, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Allele origin:
unknown
|
Counsyl
Accession: SCV000488375.1
Submitted: (Nov 23, 2016) |
|
|
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
Allele origin:
unknown
|
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894156.1
Submitted: (Nov 14, 2018) |
|
|
Pathogenic
(Apr 15, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Allele origin:
germline
|
Color Health, Inc
Accession: SCV000905051.1
Submitted: (Nov 06, 2018) |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: case-control
|
Squamous cell carcinoma of the head and neck
Allele origin:
somatic
|
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450483.1
Submitted: (Dec 08, 2020) |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: case-control
|
Colorectal cancer
Allele origin:
somatic
|
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450484.1
Submitted: (Dec 08, 2020) |
|
|
Pathogenic
(Oct 21, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Allele origin:
germline
|
Invitae
Accession: SCV000261917.9
Submitted: (Jan 07, 2021) |
Comment:
This sequence change replaces arginine with histidine at codon 175 of the TP53 protein (p.Arg175His). The arginine residue is highly conserved and there is a … (more)
This sequence change replaces arginine with histidine at codon 175 of the TP53 protein (p.Arg175His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs28934578, ExAC 0.001%). This variant has been observed in individuals and families affected with Li-Fraumeni syndrome, osteosarcoma, breast cancer and ovarian carcinoma (PMID: 8825920, 8164043, 21761402, 22006311, 16401470). ClinVar contains an entry for this variant (Variation ID: 12374). This is a well-studied variant, located in a known mutation hotspot within the central DNA-binding domain of TP53 (PMID: 23263379, 20516128, 24573247, 12007217). It causes not only loss of the tumor suppressor function of the TP53 protein, but also oncogenic gain-of-function (PMID: 23792586, 23263379). In addition, a mouse model of Li-Fraumeni syndrome was engineered using this missense variant (PMID: 15607980, 15607981), and these mice developed a variety of carcinomas and reproduced the metastatic phenotype. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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: SCV001906154.1 Submitted: (Sep 20, 2021) |
|
|
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: SCV001959136.1 Submitted: (Sep 30, 2021) |
|
|
Pathogenic
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189994.1
Submitted: (Aug 08, 2014) |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000692083.1
Submitted: (Oct 31, 2017) |
|
|
Likely pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Neoplasm of ovary
Allele origin:
somatic
|
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne
Accession: SCV000923920.1
Submitted: (Feb 22, 2019) |
|
|
Pathogenic
(Aug 01, 2005)
|
no assertion criteria provided
Method: literature only
|
LI-FRAUMENI SYNDROME 1
Allele origin:
germline
|
OMIM
Accession: SCV000033420.4
Submitted: (Dec 30, 2010) |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001551443.1 Submitted: (Mar 31, 2021) |
Comment:
The TP53 p.Arg175His variant was identified in 14 of 2378 proband chromosomes (frequency: 0.006) from individuals or families with Li Fraumeni syndrome, breast, ovarian and/or … (more)
The TP53 p.Arg175His variant was identified in 14 of 2378 proband chromosomes (frequency: 0.006) from individuals or families with Li Fraumeni syndrome, breast, ovarian and/or colon cancer (Walsh 2011, Melhem-Bertrandt 2012, Wong 2006, Bougeard 2008, Damineni 2014). This variant has also been identified in a child diagnosed with adrenocortical carcinoma at 6 months of age (Choong 2012) and a family that includes two individuals diagnosed with childhood sarcomas and four individuals diagnosed with brain tumours (Varley 1995). The variant was identified in dbSNP and ClinVar (classified as pathogenic by GeneDx, Invitae, Ambry Genetics, and 8 other submitters) . The variant was identified in control databases in 1 of 251276 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European (non-Finnish) population in 1 of 113600 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The R175 residue is a mutation hotspot and results in a structurally unstable, unfolded p53 protein (Xu 2014). The R175H variant has been shown to confer oncogenic gain of function to the p53 protein by multiple studies (Petitjean 2007, Capponcelli 2005), which is hypothesized to occur via the increased activation of the c-Met receptor tyrosine kinase and/or the inactivation of the ATM-dependent DNA damage response, resulting in a defective G2/M checkpoint (Grugan 2013, Liu 2010). The p.Arg175 residue is conserved across mammals and other organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the His variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
|
|
Pathogenic
(Jul 29, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Esophageal cancer
(Somatic mutation)
Allele origin:
somatic
|
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV000297733.1
Submitted: (Aug 09, 2016) |
Comment:
SIFT:Deleterious (score: 0) MutationTaster:Disease causing (p-value: 1)
|
|
Likely pathogenic
(Jul 14, 2015)
|
no assertion criteria provided
Method: literature only
|
Neoplasm
(Somatic mutation)
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504891.1
Submitted: (Jul 18, 2016) |
|
|
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: SCV001432233.1
Submitted: (Feb 01, 2020) |
|
|
Pathogenic
(Mar 19, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Allele origin:
somatic
|
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738476.1
Submitted: (May 19, 2021) |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808819.1 Submitted: (Aug 24, 2021) |
|
|
not provided
(Mar 10, 2016)
|
no assertion provided
Method: literature only
|
Breast neoplasm
(Somatic mutation)
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504892.1
Submitted: (Jul 18, 2016) |
|
Functional evidence
Help| Functional consequence | Method | Result | Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
variation affecting protein function
|
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV000297733.1
Submitted: (Aug 09, 2016)
|
|
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| 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 |
| Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. | Mandelker D | JAMA | 2017 | PMID: 28873162 |
| Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. | Nykamp K | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28492532 |
| The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. | Stenson PD | Human genetics | 2017 | PMID: 28349240 |
| Multiple primary tumors in a family with Li-Fraumeni syndrome with a TP53 germline mutation identified by next-generation sequencing. | Zampiga V | The International journal of biological markers | 2016 | PMID: 27516001 |
| Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome. | Park KJ | Annals of laboratory medicine | 2016 | PMID: 27374712 |
| Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
| 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 |
| Heterogeneity of Li-Fraumeni syndrome links to unequal gain-of-function effects of p53 mutations. | Xu J | Scientific reports | 2014 | PMID: 24573247 |
| A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion. | Grugan KD | Cancer biology & therapy | 2013 | PMID: 23792586 |
| p53 mutations in cancer. | Muller PA | Nature cell biology | 2013 | PMID: 23263379 |
| The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis. | Leroy B | Nucleic acids research | 2013 | PMID: 23161690 |
| p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. | Jackson JG | Cancer cell | 2012 | PMID: 22698404 |
| Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. | Choong SS | Clinical genetics | 2012 | PMID: 22233476 |
| Early onset HER2-positive breast cancer is associated with germline TP53 mutations. | Melhem-Bertrandt A | Cancer | 2012 | PMID: 21761402 |
| Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. | Walsh T | Proceedings of the National Academy of Sciences of the United States of America | 2011 | PMID: 22006311 |
| 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(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. | Kogan-Sakin I | Cell death and differentiation | 2011 | PMID: 20689556 |
| The tumor suppressor p53: from structures to drug discovery. | Joerger AC | Cold Spring Harbor perspectives in biology | 2010 | PMID: 20516128 |
| Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation. | Malcikova J | Biological chemistry | 2010 | PMID: 20128691 |
| A common gain of function of p53 cancer mutants in inducing genetic instability. | Liu DP | Oncogene | 2010 | PMID: 19881536 |
| Genetic counseling can influence the course of a suspected familial cancer syndrome patient: from a case of Li-Fraumeni like syndrome with a germline mutation in the TP53 gene. | Hwang SM | The Korean journal of laboratory medicine | 2008 | PMID: 19127115 |
| Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. | Bougeard G | Journal of medical genetics | 2008 | PMID: 18511570 |
| p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. | Kawauchi K | Nature cell biology | 2008 | PMID: 18391940 |
| 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 clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. | Olivier M | Clinical cancer research : an official journal of the American Association for Cancer Research | 2006 | PMID: 16489069 |
| Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. | Wong P | Gastroenterology | 2006 | PMID: 16401470 |
| Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation. | Capponcelli S | Human mutation | 2005 | PMID: 15977174 |
| Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. | Lang GA | Cell | 2004 | PMID: 15607981 |
| Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. | Olive KP | Cell | 2004 | PMID: 15607980 |
| 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 |
| Germline TP53 mutations and Li-Fraumeni syndrome. | Varley JM | Human mutation | 2003 | PMID: 12619118 |
| The IARC TP53 database: new online mutation analysis and recommendations to users. | Olivier M | Human mutation | 2002 | PMID: 12007217 |
| Role of the p53-homologue p73 in E2F1-induced apoptosis. | Stiewe T | Nature genetics | 2000 | PMID: 11101847 |
| A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li-Fraumeni patients carrying a mutation to the TP53 gene. | Varley JM | Oncogene | 1997 | PMID: 9047394 |
| An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. | Varley JM | Journal of medical genetics | 1995 | PMID: 8825920 |
| Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. | McIntyre JF | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 1994 | PMID: 8164043 |
| http://docm.genome.wustl.edu/variants/ENST00000269305:c.524G>A | - | - | - | - |
Text-mined citations for rs28934578...
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Record last updated Oct 02, 2021