ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- reviewed by expert panel FDA Recognized Database
- Submissions:
- 56
- First in ClinVar:
- Apr 8, 2013
- Most recent Submission:
- Apr 15, 2023
- Last evaluated:
- Aug 28, 2019
- Accession:
- VCV000012366.51
- Variation ID:
- 12366
- Description:
- single nucleotide variant
Help
NM_000546.6(TP53):c.818G>A (p.Arg273His)
- Allele ID
- 27405
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17p13.1
- Genomic location
- 17: 7673802 (GRCh38) GRCh38 UCSC
- 17: 7577120 (GRCh37) GRCh37 UCSC
- HGVS
-
Nucleotide Protein Molecular
consequenceNM_000546.6:c.818G>A MANE Select NP_000537.3:p.Arg273His missense NM_000546.5(TP53):c.818G>A NM_001126112.3:c.818G>A NP_001119584.1:p.Arg273His missense NM_001126113.3:c.818G>A NP_001119585.1:p.Arg273His missense NM_001126114.3:c.818G>A NP_001119586.1:p.Arg273His missense NM_001126115.2:c.422G>A NP_001119587.1:p.Arg141His missense NM_001126116.2:c.422G>A NP_001119588.1:p.Arg141His missense NM_001126117.2:c.422G>A NP_001119589.1:p.Arg141His missense NM_001126118.2:c.701G>A NP_001119590.1:p.Arg234His missense NM_001276695.3:c.701G>A NP_001263624.1:p.Arg234His missense NM_001276696.3:c.701G>A NP_001263625.1:p.Arg234His missense NM_001276697.3:c.341G>A NP_001263626.1:p.Arg114His missense NM_001276698.3:c.341G>A NP_001263627.1:p.Arg114His missense NM_001276699.3:c.341G>A NP_001263628.1:p.Arg114His missense NM_001276760.3:c.701G>A NP_001263689.1:p.Arg234His missense NM_001276761.3:c.701G>A NP_001263690.1:p.Arg234His missense NC_000017.11:g.7673802C>T NC_000017.10:g.7577120C>T NG_017013.2:g.18749G>A LRG_321:g.18749G>A LRG_321t1:c.818G>A LRG_321p1:p.Arg273His LRG_321t5:c.422G>A LRG_321p5:p.Arg141His P04637:p.Arg273His - Protein change
- R273H, R141H, R234H, R114H
- Other names
- p.R273H:CGT>CAT
- Canonical SPDI
- NC_000017.11:7673801:C:T
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- 0.00020 (T)
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.00002
- 1000 Genomes Project 0.00020
- Links
- ClinGen: CA000434
- UniProtKB: P04637#VAR_005995
- OMIM: 191170.0020
- dbSNP: rs28934576
- VarSome
Help
Aggregate interpretations per condition
Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
---|---|---|---|---|---|
Pathogenic | 4 | reviewed by expert panel | Aug 28, 2019 | RCV000463420.12 | |
Pathogenic/Likely pathogenic | 7 | criteria provided, multiple submitters, no conflicts | Sep 1, 2022 | RCV000013163.29 | |
Pathogenic/Likely pathogenic | 3 | criteria provided, multiple submitters, no conflicts | Aug 24, 2021 | RCV000115738.13 | |
Pathogenic | 6 | criteria provided, multiple submitters, no conflicts | Apr 29, 2022 | RCV000254693.19 | |
Pathogenic | 2 | criteria provided, single submitter | - | RCV000422097.3 | |
Pathogenic | 2 | criteria provided, single submitter | Jun 6, 2022 | RCV000431361.3 | |
Pathogenic | 1 | criteria provided, single submitter | Mar 14, 2022 | RCV002476955.1 | |
Pathogenic | 1 | no assertion criteria provided | Jan 1, 1993 | RCV000013164.6 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424109.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000419960.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000418930.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000422733.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424218.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000439513.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000440815.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424833.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000443907.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000423826.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424627.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000428779.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000429822.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000430161.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000433409.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000435547.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000434044.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000437210.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000436207.2 | |
Likely pathogenic | 1 | no assertion criteria provided | Jul 14, 2015 | RCV000441169.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000440474.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444851.2 | |
Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444900.2 | |
Pathogenic/Likely pathogenic | 2 | no assertion criteria provided | Mar 19, 2021 | RCV000785345.4 | |
Pathogenic | 1 | no assertion criteria provided | Sep 1, 2020 | RCV001257517.2 | |
Pathogenic | 1 | no assertion criteria provided | Mar 19, 2021 | RCV001527470.2 | |
Pathogenic | 1 | no assertion criteria provided | - | RCV001358389.2 | |
Pathogenic | 1 | no assertion criteria provided | Mar 19, 2021 | RCV001527484.2 | |
Pathogenic | 1 | no assertion criteria provided | Jul 1, 2021 | RCV003162246.1 |
Help
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
---|---|---|---|---|---|---|
HI score Help | TS score Help | Within gene | All | |||
TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2836 | 2931 |
Submitted interpretations and evidence
HelpInterpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
---|---|---|---|---|---|
Pathogenic
(Aug 28, 2019)
|
reviewed by expert panel
Method: curation
|
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen TP53 Variant Curation Expert Panel,ClinGen
FDA Recognized Database
Accession: SCV001142550.1 First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Comment:
This variant is within a codon that is an established hotspot in the TP53 gene (PM1; PMID: 2046748). This variant has a BayesDel score > … (more)
This variant is within a codon that is an established hotspot in the TP53 gene (PM1; PMID: 2046748). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 15 or higher (PP3). Transactivation assays show a low functioning allele according to Kato, et al. and there is evidence of a dominant negative effect and loss of function according to Giacomelli, et al. (PS3; PMID: 12826609, 30224644). This variant has been reported in at least 2 probands meeting classic Li-Fraumeni syndrome criteria and 4 probands meeting Chompret criteria (PS4; PMID: 16401470, 15390294, 9242456, 10864200, 1565144, 7732013). Additionally, there is a de novo observation of a proband with breast cancer at age 29 with parental confirmation (PS2; PMID: 12672316). In summary, TP53 c.818G>A; p.Arg273His meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM1, PP3, PS3, PS4, PS2. (less)
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Pathogenic
(Jan 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001735236.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
This missense variant replaces arginine with histidine at codon 273 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant … (more)
This missense variant replaces arginine with histidine at codon 273 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown the mutant protein to be non-functional in transactivation assays (IARC database, PMID: 12826609, 20407015, 25584008) and cell growth assays (PMID: 24677579, 25584008, 29979965, 30224644). This variant has been reported in individuals affected with classic Li-Fraumeni syndrome (PMID: 1565144, 7732013, 10864200, 15390294, 16401470, 27374712) and in individuals meeting the Chompret criteria for Li-Fraumeni syndrome (PMID: 9242456, 25584008, 25787918). This variant has been identified in 4/251054 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Mar 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605425.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 08, 2022 |
Comment:
The TP53 c.818G>A, p.Arg273His variant (rs28934576), has been reported in multiple patients diagnosed with Li-Fraumeni syndrome (Curry 2011, Khayat 2004, Malkin 1992, Park 2016, Schlegelberger … (more)
The TP53 c.818G>A, p.Arg273His variant (rs28934576), has been reported in multiple patients diagnosed with Li-Fraumeni syndrome (Curry 2011, Khayat 2004, Malkin 1992, Park 2016, Schlegelberger 2015, Siddiqui 2005, Tsaousis 2019, Zerdoumi 2012). Functional characterization of the variant protein indicates a defect in the transactivation of TP53 targets (Malcikova 2010, Monti 2007, Monti 2011, Zerdoumi 2012) and repression of genes involved in cell proliferation (Scian 2004). This results in an increase in growth, invasiveness, and resistance to apoptosis of cell lines upon DNA damage (Kalo 2012, Li 2014). This variant is found in the general population with an allele frequency of 0.0016% (4/251054 alleles) in the Genome Aggregation Database. The arginine at residue 273 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.868). Based on the above information, the variant is classified as pathogenic. References: Curry S et al. Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation. Pediatr Dev Pathol. 2011; 14(3):248-51. Kalo E et al. Mutant p53R273H attenuates the expression of phase 2 detoxifying enzymes and promotes the survival of cells with high levels of reactive oxygen species. J Cell Sci. 2012; 125(Pt 22):5578-86. Khayat C et al. Rhabdomyosarcoma, osteosarcoma, and adrenocortical carcinoma in a child with a germline p53 mutation. Pediatr Blood Cancer. 2004; 43(6):683-6. Li J et al. Mutants TP53 p.R273H and p.R273C but not p.R273G enhance cancer cell malignancy. Hum Mutat. 2014; 35(5):575-84. Malcikova J et al. Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation. Biol Chem. 2010; 391(2-3):197-205. Malkin D et al. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med. 1992; 326(20):1309-15. Monti P et al. Transcriptional functionality of germ line p53 mutants influences cancer phenotype. Clin Cancer Res. 2007; 13(13):3789-95. Monti P et al. Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Mol Cancer Res. 2011; 9(3):271-9. Schlegelberger B et al. A child with Li-Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies. Pediatr Blood Cancer. 2015; 62(8):1481-4. Scian M et al. Modulation of gene expression by tumor-derived p53 mutants. Cancer Res. 2004; 64(20):7447-54. Siddiqui R et al. The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. Fam Cancer. 2005; 4(2):177-81. Tsaousis GN et al. Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. BMC Cancer. 2019 Jun 3;19(1):535. Zerdoumi Y et al. Drastic effect of germline TP53 missense mutations in Li-Fraumeni patients. Hum Mutat. 2013; 34(3):453-61. (less)
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Pathogenic
(Sep 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002572762.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). It is located in a mutational hot … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). It is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 12826609 , 30224644). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87; 3Cnet: 1.00). The variant has been previously reported as de novo in a similarly affected individual (PMID: 12672316). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 10864200 , 15390294 , 1565144 , 16401470 , 7732013 , 9242456). Different missense changes at the same codon (p.Arg273Cys, p.Arg273Gly, p.Arg273Leu, p.Arg273Pro, p.Arg273Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000043594 , VCV000231060 , VCV000376655 , VCV000376656 , VCV000634682). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Osteosarcoma (present)
Zygosity: 1 Single Heterozygote
|
|
Pathogenic
(Jul 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000839110.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
|
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Likely pathogenic
(Feb 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000677727.2
First in ClinVar: Oct 19, 2014 Last updated: Dec 24, 2022 |
|
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Pathogenic
(Jun 06, 2022)
|
criteria provided, single submitter
Method: research
|
Lung adenocarcinoma
Affected status: yes
Allele origin:
somatic
|
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
Accession: SCV003806294.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Apr 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149647.15
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
Not observed at a significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity … (more)
Not observed at a significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Kato 2003, Monti 2011, Wasserman 2015, Kotler 2018); This variant is associated with the following publications: (PMID: 23334668, 20128691, 7732013, 10864200, 18511570, 25896519, 23484829, 29324801, 32039725, 15492269, 17606709, 22811390, 23559009, 22899716, 24573247, 24677579, 25958320, 26703669, 17636407, 25433984, 26332594, 8423216, 20693561, 21054160, 1565144, 21552135, 21484931, 25584008, 23172776, 17540308, 27798748, 25530302, 27498048, 27323394, 27287813, 27346245, 27659839, 27374712, 28091804, 27501770, 25787918, 1447251, 9242456, 12672316, 16401470, 28509937, 20522432, 27831900, 26225655, 26681312, 28453743, 21761402, 16096528, 29489754, 28472496, 21343334, 26585234, 28861920, 29752822, 15607980, 30287823, 30720243, 30092803, 30840781, 31159747, 15951970, 22851211, 28369373, 31105275, 32475984, 32156018, 33300245, 34308366, 32817165, 33372952, 31958074, 33332384, 33245408, 32427313, 33087929, 33144694, 29979965, 15510160) (less)
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Pathogenic
(Feb 09, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697450.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The TP53 c.818G>A (p.Arg273His) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. … (more)
Variant summary: The TP53 c.818G>A (p.Arg273His) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 3/114148 control chromosomes at a frequency of 0.0000263, which does not exceed the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398). The variant has been reported in numerous affected individuals in the literature and the codon location is a known hotspot mutation occurring as a frequent mutation in affected individuals. Functional studies report a dominant negative affect of the variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Likely pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000821786.2
First in ClinVar: Oct 10, 2018 Last updated: May 04, 2020 |
Comment:
This sequence change replaces Arginine with Histidine at codon 273 of the TP53 protein. The arginine residue is highly conserved among species and is located … (more)
This sequence change replaces Arginine with Histidine at codon 273 of the TP53 protein. The arginine residue is highly conserved among species and is located in a functional domain of the protein which interacts with multiple proteins. There is a large physiochemical difference between arginine and histidine (Grantham Score 29). There is a large physiochemical difference between arginine and tryptophan (Grantham Score 101).This variant is present in population databases at a very low frequency ( rs28934576, ExAC 0.02%) and has been reported in multiple individuals and families affected with Li-Fraumeni and Li-Fraumeni-like syndromes (PMID: 17540308, 1565144, 20693561). Algorithms developed to predict the effect of missense changes on protein structure and function suggest that this variant is likely to be damaging to the protein. In addition, experimental studies have shown that this variant affects TP53 transactivation activity at variable levels(PMID: 12826609). In summary, this is a rare sequence change that is expected to affect the TP53 protein and cause disease.The mutation database Clinvar contains entries for this variant (Variation ID: 12366) (less)
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Pathogenic
(-)
|
criteria provided, single submitter
Method: case-control
|
Squamous cell carcinoma of the head and neck
Affected status: yes
Allele origin:
somatic
|
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450494.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Age: 50-59 years
Sex: male
Geographic origin: Sri Lanka
|
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Pathogenic
(Dec 15, 2020)
|
criteria provided, single submitter
Method: research
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
Department of Pediatrics,Memorial Sloan Kettering Cancer Center
Accession: SCV001478190.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
|
Pathogenic
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762058.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
Clinical Features:
Breast carcinoma (present)
Sex: female
|
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Pathogenic
(Apr 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000602280.2
First in ClinVar: Sep 28, 2017 Last updated: Jan 01, 2022 |
|
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Pathogenic
(Nov 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
Centogene AG - the Rare Disease Company
Accession: SCV002059231.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
|
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Pathogenic
(Apr 03, 2019)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002072052.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the TP53 gene demonstrated a sequence change, c.818G>A, in exon 8 that results in an amino acid change, p.Arg273His. This sequence … (more)
DNA sequence analysis of the TP53 gene demonstrated a sequence change, c.818G>A, in exon 8 that results in an amino acid change, p.Arg273His. This sequence change has been described in the gnomAD database with a low global population frequency of 0.01% (dbSNP rs28934576). This pathogenic sequence change has previously been described in multiple patients and families with Li Fraumeni syndrome (PMIDs: 1565144, 21054160, 25584008). The p.Arg273His change affects a highly conserved amino acid residue located in a domain of the TP53 protein that is known to be functional. The p.Arg273 amino acid residue has multiple other amino acid substitutions that are reported to be pathogenic, including p.Arg273Leu, p.Arg273Gly, p.Arg273Ser, and p.Arg273Cys (PMIDs: 10864200, 8425176, 8164043, 8479749). Functional assays demonstrate that the p.Arg273His change results in deficient transactivation activity and results in a dominant negative effect over wild-type p53 (PMIDs: 12826609, 17636407). The p.Arg273His substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). (less)
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Pathogenic
(Aug 24, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186052.8
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
Comment:
The p.R273H pathogenic mutation (also known as c.818G>A), located in coding exon 7 of the TP53 gene, results from a G to A substitution at … (more)
The p.R273H pathogenic mutation (also known as c.818G>A), located in coding exon 7 of the TP53 gene, results from a G to A substitution at nucleotide position 818. The arginine at codon 273 is replaced by histidine, an amino acid with highly similar properties. This alteration occurs at a well-characterized mutation "hotspot" located within the functionally critical DNA binding domain, and is associated with a classic LFS-associated tumor spectrum, including soft tissue and osteosarcomas, breast cancer, and central nervous system malignancies (Petitjean A et al. IARC TP53 database [version R16, November 2012]. Hum. Mutat. 2007 Jun;28(6):622-9). To date, the p.R273H mutation has been detected in numerous individuals/families satisfying classic criteria for LFS and has segregated with disease in all families with multiple informative relatives tested (Ambry internal data). 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). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (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 observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
|
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Pathogenic
(Sep 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
New York Genome Center
Accession: SCV002764339.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The c.818G>A, p.Arg273His missense variant in TP53 has been reported in several individuals meeting classic Li-Fraumeni or Chompret criteria,occurring de novo in at least one … (more)
The c.818G>A, p.Arg273His missense variant in TP53 has been reported in several individuals meeting classic Li-Fraumeni or Chompret criteria,occurring de novo in at least one individual and segregating with disease in affected families (PMID: 9242456, 21484931, 17540308, 1565144, 20693561, 21552135). This variant is located in the DNA-binding domain of the TP53 protein and is defined as a contact mutation that eliminates an essential DNA contact (PMID: 20516128). A mutant mouse model for this variant develops various tumors and carcinomas by recapitulating LFS (PMID: 15607980). In addition, experimental studies have shown that this variant disrupts transcriptional activity in yeast-based assays (PMID: 12826609) and enhances cell proliferation, invasion, migration, and drug resistance in vitro (PMID:17636407, 24677579). This variant has three heterozygous alleles in the gnomAD v3.1.1 database, suggesting it is not a common benign variant in the populations represented in this database. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, this variant is classified as pathogenic. (less)
Clinical Features:
Hepatic steatosis (present) , Type 2 diabetes mellitus (present) , Hyperlipidemia (present)
Zygosity: 1 Single Heterozygote
Secondary finding: yes
|
|
Pathogenic
(Mar 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Colorectal cancer Hepatocellular carcinoma Glioma susceptibility 1 Li-Fraumeni syndrome 1 Adrenocortical carcinoma, hereditary Bone osteosarcoma Carcinoma of pancreas Choroid plexus papilloma Nasopharyngeal carcinoma Basal cell carcinoma, susceptibility to, 7 Bone marrow failure syndrome 5
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611327.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Oct 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000545317.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 273 of the TP53 protein (p.Arg273His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 273 of the TP53 protein (p.Arg273His). 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 clinical features of Li-Fraumeni syndrome (LFS) (PMID: 1565144, 9242456, 17540308, 20693561, 21484931, 21552135). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12366). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 01, 1993)
|
no assertion criteria provided
Method: literature only
|
LI-FRAUMENI SYNDROME 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000033410.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 08, 2013 |
Comment on evidence:
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was … (more)
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was a male in whom soft-tissue sarcoma was discovered at the age of 22 years and gastric carcinoma at the age of 30 years (see LFS; 151623). In 5 of 6 anaplastic carcinomas of the thyroid and in an anaplastic carcinoma thyroid cell line ARO, Fagin et al. (1993) identified the R273H mutation. The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggested that inactivation of p53 may confer these neoplasms with aggressive properties and may further loss of differentiated function. (less)
|
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Pathogenic
(Jan 01, 1993)
|
no assertion criteria provided
Method: literature only
|
THYROID CARCINOMA, ANAPLASTIC, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000033411.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 08, 2013 |
Comment on evidence:
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was … (more)
Malkin et al. (1992) identified a germline CGT-to-CAT mutation in exon 8 of the p53 gene that converted arg273 to his (R273H). The proband was a male in whom soft-tissue sarcoma was discovered at the age of 22 years and gastric carcinoma at the age of 30 years (see LFS; 151623). In 5 of 6 anaplastic carcinomas of the thyroid and in an anaplastic carcinoma thyroid cell line ARO, Fagin et al. (1993) identified the R273H mutation. The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggested that inactivation of p53 may confer these neoplasms with aggressive properties and may further loss of differentiated function. (less)
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|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Acute myeloid leukemia
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504664.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Prostate adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504665.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Malignant melanoma of skin
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504666.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Hepatocellular carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504667.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Neoplasm of brain
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504668.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Brainstem glioma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504669.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Neoplasm of the large intestine
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504670.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Multiple myeloma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504671.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Carcinoma of esophagus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504672.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Breast neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504673.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Adrenal cortex carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504674.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504675.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Squamous cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504676.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Ovarian serous cystadenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504677.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504678.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504679.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Transitional cell carcinoma of the bladder
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504680.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Medulloblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504681.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
B-cell chronic lymphocytic leukemia
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504682.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504683.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(Jul 14, 2015)
|
no assertion criteria provided
Method: literature only
|
Neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504684.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Uterine carcinosarcoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504685.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV000692068.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
|
Pathogenic
(Sep 01, 2020)
|
no assertion criteria provided
Method: provider interpretation
|
Rhabdomyosarcoma
Affected status: yes
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434343.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
|
|
Pathogenic
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000190004.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Pancreatic adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504661.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504662.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000504663.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Neoplasm of ovary
Affected status: yes
Allele origin:
somatic
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923913.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
Observation 1: Observation 2: |
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001554107.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The TP53 p.Arg273His variant was identified in 2 of 942 proband chromosomes (frequency: 0.002) from individuals or families with Li Fraumeni Syndrome or thyroid cancer … (more)
The TP53 p.Arg273His variant was identified in 2 of 942 proband chromosomes (frequency: 0.002) from individuals or families with Li Fraumeni Syndrome or thyroid cancer (Masciari 2011, Romei 2017) and reported in multiple case studies in individuals or families with Li-Fraumeni Syndrome (Bemis 2007, Sugawara 2011, Baumuller 2010). In addition, the variant was reported as a somatic mutation in breast cancer, colorectal cancer, non-small cell lung cancer or high-grade glioma tissues (Jiang 2018, Heath-2018, Li 2018). The variant was also identified in dbSNP (ID: rs28934576) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, GeneDx, Ambry Genetics and eight other submitters; as likely pathogenic by two submitters), and in LOVD 3.0 (2x as pathogenic). The variant was identified in control databases in 4 of 245868 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 3 of 111470 chromosomes (freq: 0.00003), Ashkenazi Jewish in 1 of 9842 chromosomes (freq: 0.0001), but not in the African, Other, Latino, East Asian, Finnish, or South Asian populations. Several functional studies suggests the variant enhances cell migration, invasion abilities, influences apoptosis, leads to more aggressive phenotypes, and enhances cancer cell malignancy (Kang 2018, Joerger 2010, Dong 2007, Li 2014). The p.Arg273 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
Number of individuals with the variant: 1
|
|
Pathogenic
(Mar 19, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Multiple myeloma
Colorectal cancer
Affected status: yes
Allele origin:
somatic
|
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738487.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021
Comment:
Related to multiple myeloma
|
Secondary finding: yes
|
|
Pathogenic
(Mar 19, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Neoplasm of ovary
Affected status: no
Allele origin:
somatic
|
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738490.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021 |
Secondary finding: yes
|
|
Pathogenic
(Mar 19, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: no
Allele origin:
somatic
|
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738505.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021 |
Secondary finding: yes
|
|
Pathogenic
(Jul 01, 2021)
|
no assertion criteria provided
Method: research
|
Gastric cancer
Affected status: unknown
Allele origin:
germline
|
Laboratory for Genotyping Development, RIKEN
Accession: SCV002758479.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
|
Functional evidence
HelpThere 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
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group. | Li H | Journal of the National Cancer Institute | 2021 | PMID: 33372952 |
Identifying sequence variants contributing to hereditary breast and ovarian cancer in BRCA1 and BRCA2 negative breast and ovarian cancer patients. | Jarhelle E | Scientific reports | 2019 | PMID: 31882575 |
Nucleotide variants and protein expression of TP53 in a Sri Lankan cohort of patients with head and neck cancer. | Manoharan V | Molecular medicine reports | 2019 | PMID: 30816478 |
Mutational processes shape the landscape of TP53 mutations in human cancer. | Giacomelli AO | Nature genetics | 2018 | PMID: 30224644 |
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. | Kotler E | Molecular cell | 2018 | PMID: 29979965 |
The landscape of genomic alterations across childhood cancers. | Gröbner SN | Nature | 2018 | PMID: 29489754 |
Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. | Mandelker D | JAMA | 2017 | PMID: 28873162 |
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. | Nykamp K | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28492532 |
Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. | Kline CN | Neuro-oncology | 2017 | PMID: 28453743 |
Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome. | Park KJ | Annals of laboratory medicine | 2016 | PMID: 27374712 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. | Chang MT | Nature biotechnology | 2016 | PMID: 26619011 |
Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
A child with Li-Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies. | Schlegelberger B | Pediatric blood & cancer | 2015 | PMID: 25787918 |
Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study. | Wasserman JD | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2015 | PMID: 25584008 |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
Mutants TP53 p.R273H and p.R273C but not p.R273G enhance cancer cell malignancy. | Li J | Human mutation | 2014 | PMID: 24677579 |
Prognostic significance of TP53 mutations and single nucleotide polymorphisms in acute myeloid leukemia: a case series and literature review. | Zeichner SB | Asian Pacific journal of cancer prevention : APJCP | 2014 | PMID: 24641375 |
Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. | Kihara R | Leukemia | 2014 | PMID: 24487413 |
Haploinsufficiency of del(5q) genes, Egr1 and Apc, cooperate with Tp53 loss to induce acute myeloid leukemia in mice. | Stoddart A | Blood | 2014 | PMID: 24381225 |
The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis. | Leroy B | Nucleic acids research | 2013 | PMID: 23161690 |
BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. | Pennington KP | Cancer | 2013 | PMID: 22811390 |
Mutant p53R273H attenuates the expression of phase 2 detoxifying enzymes and promotes the survival of cells with high levels of reactive oxygen species. | Kalo E | Journal of cell science | 2012 | PMID: 22899716 |
Early onset HER2-positive breast cancer is associated with germline TP53 mutations. | Melhem-Bertrandt A | Cancer | 2012 | PMID: 21761402 |
Gastric cancer in individuals with Li-Fraumeni syndrome. | Masciari S | Genetics in medicine : official journal of the American College of Medical Genetics | 2011 | PMID: 21552135 |
Association of germline or somatic TP53 missense mutation with oncogene amplification in tumors developed in patients with Li-Fraumeni or Li-Fraumeni-like syndrome. | Sugawara W | Genes, chromosomes & cancer | 2011 | PMID: 21484931 |
Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. | Monti P | Molecular cancer research : MCR | 2011 | PMID: 21343334 |
Sebaceous gland carcinoma of the eyelid masquerading as a cutaneous horn in Li--Fraumeni syndrome. | Baumüller S | The British journal of ophthalmology | 2011 | PMID: 20693561 |
The tumor suppressor p53: from structures to drug discovery. | Joerger AC | Cold Spring Harbor perspectives in biology | 2010 | PMID: 20516128 |
Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation. | Malcikova J | Biological chemistry | 2010 | PMID: 20128691 |
Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. | Bougeard G | Journal of medical genetics | 2008 | PMID: 18511570 |
p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells. | Dong P | Clinical & experimental metastasis | 2007 | PMID: 17636407 |
Transcriptional functionality of germ line p53 mutants influences cancer phenotype. | Monti P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2007 | PMID: 17606709 |
EGFR-mutant lung adenocarcinoma in a patient with Li-Fraumeni syndrome. | Bemis LT | The Lancet. Oncology | 2007 | PMID: 17540308 |
The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. | Olivier M | Clinical cancer research : an official journal of the American Association for Cancer Research | 2006 | PMID: 16489069 |
Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. | Wong P | Gastroenterology | 2006 | PMID: 16401470 |
The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. | Siddiqui R | Familial cancer | 2005 | PMID: 15951970 |
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. | Olive KP | Cell | 2004 | PMID: 15607980 |
Rhabdomyosarcoma, osteosarcoma, and adrenocortical carcinoma in a child with a germline p53 mutation. | Khayat CM | Pediatric blood & cancer | 2004 | PMID: 15390294 |
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. | Kato S | Proceedings of the National Academy of Sciences of the United States of America | 2003 | PMID: 12826609 |
Prediction of pathogenic mutations in patients with early-onset breast cancer by family history. | Lalloo F | Lancet (London, England) | 2003 | PMID: 12672316 |
P53 germline mutations in childhood cancers and cancer risk for carrier individuals. | Chompret A | British journal of cancer | 2000 | PMID: 10864200 |
Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. | Berns EM | British journal of cancer | 1998 | PMID: 9569050 |
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. | Varley JM | Cancer research | 1997 | PMID: 9242456 |
A simple p53 functional assay for screening cell lines, blood, and tumors. | Flaman JM | Proceedings of the National Academy of Sciences of the United States of America | 1995 | PMID: 7732013 |
High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. | Fagin JA | The Journal of clinical investigation | 1993 | PMID: 8423216 |
Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. | Malkin D | The New England journal of medicine | 1992 | PMID: 1565144 |
http://docm.genome.wustl.edu/variants/ENST00000269305:c.818G>A | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8d32df42-16ac-41f2-9bf1-e2b9ce206190 | - | - | - | - |
Text-mined citations for rs28934576...
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Record last updated Jun 04, 2023