The p.R196* pathogenic mutation (also known as c.586C>T), located in coding exon 5 of the TP53 gene, results from a C to T substitution at nucleotide position 586. This changes the amino acid from an arginine to a stop codon within coding exon 5. This mutation has been reported in a number of individuals with early onset or multiple cancers and in some families who meet either classic diagnostic criteria or Chompret criteria for Li-Fraumeni syndrome (LFS) (Vahteristo P et al. Cancer Research. 2001 Aug;61:5718-5722; Pinto C et al. Fam. Cancer 2009 May;8:383-90; Melhem-Bertrandt A et al. Cancer. 2012 Feb;118(4):908-13; Mitchell G et al. PLoS One. 2013 Jul;8(7):e69026; Villani A et al. Lancet Oncol. 2016 Sep;17:1295-305; Saya S et al. Fam Cancer. 2017 Jul;16(3):433-440). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
NM_000546.6(TP53):c.586C>T (p.Arg196Ter)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic
Pathogenic (19)
Pathogenic (19)
19 out of 24 submissions contributed to this classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
24
Somatic
Clinical impact
Help
criteria provided, single submitter. Learn more about how ClinVar calculates review status.
This classification is based on the single submission received
Help
The aggregate somatic clinical impact for this variant for one or more tumor types, using the AMP/ASCO/CAP terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
1
Somatic
Oncogenicity
Help
criteria provided, single submitter. Learn more about how ClinVar calculates review status.
Oncogenic
This classification is based on the single submission received
Help
The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
1
Variant Details
- Identifiers
-
NM_000546.6(TP53):c.586C>T (p.Arg196Ter)
Variation ID: 43589 Accession: VCV000043589.57
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7674945 (GRCh38) [ NCBI UCSC ] 17: 7578263 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 1, 2016 May 3, 2026 Jun 24, 2025 Somatic - Clinical impact Nov 22, 2025 Nov 22, 2025 Jan 16, 2025 Somatic - Oncogenicity Jan 3, 2026 Jan 3, 2026 Dec 29, 2025 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000546.6:c.586C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Arg196Ter nonsense NM_001126112.3:c.586C>T NP_001119584.1:p.Arg196Ter nonsense NM_001126113.3:c.586C>T NP_001119585.1:p.Arg196Ter nonsense NM_001126114.3:c.586C>T NP_001119586.1:p.Arg196Ter nonsense NM_001126115.2:c.190C>T NP_001119587.1:p.Arg64Ter nonsense NM_001126116.2:c.190C>T NP_001119588.1:p.Arg64Ter nonsense NM_001126117.2:c.190C>T NP_001119589.1:p.Arg64Ter nonsense NM_001126118.2:c.469C>T NP_001119590.1:p.Arg157Ter nonsense NM_001276695.3:c.469C>T NP_001263624.1:p.Arg157Ter nonsense NM_001276696.3:c.469C>T NP_001263625.1:p.Arg157Ter nonsense NM_001276697.3:c.109C>T NP_001263626.1:p.Arg37Ter nonsense NM_001276698.3:c.109C>T NP_001263627.1:p.Arg37Ter nonsense NM_001276699.3:c.109C>T NP_001263628.1:p.Arg37Ter nonsense NM_001276760.3:c.469C>T NP_001263689.1:p.Arg157Ter nonsense NM_001276761.3:c.469C>T NP_001263690.1:p.Arg157Ter nonsense NC_000017.11:g.7674945G>A NC_000017.10:g.7578263G>A NG_017013.2:g.17606C>T LRG_321:g.17606C>T LRG_321t1:c.586C>T LRG_321p1:p.Arg196Ter - Protein change
- R157*, R196*, R64*, R37*
- Other names
-
p.Arg196Ter
- Canonical SPDI
- NC_000017.11:7674944:G:A
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3915 | 4016 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
May 20, 2025 | RCV000131510.19 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jun 24, 2025 | RCV000205265.33 | |
| Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Nov 9, 2022 | RCV000412710.28 | |
| Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000785329.10 | |
| Pathogenic (1) |
no assertion criteria provided
|
Mar 19, 2021 | RCV001527464.9 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 16, 2024 | RCV002288535.12 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 11, 2024 | RCV003473274.2 | |
|
TP53-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Oct 1, 2024 | RCV004797592.1 |
| Pathogenic (1) |
criteria provided, single submitter
|
May 27, 2022 | RCV005357264.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Expand all rows
Collapse all rows
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jan 26, 2017)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome |
Genetic Services Laboratory, University of Chicago
Accession: SCV000597519.1
First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(May 20, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Ambry Genetics
Accession: SCV000186503.10
First in ClinVar: Aug 06, 2014 Last updated: Jul 13, 2025 |
Comment:
show
The p.R196* pathogenic mutation (also known as c.586C>T), located in coding exon 5 of the TP53 gene, results from a C to T substitution at nucleotide position 586. This changes the amino acid from an arginine to a stop codon within coding exon 5. This mutation has been reported in a number of individuals with early onset or multiple cancers and in some families who meet either classic diagnostic criteria or Chompret criteria for Li-Fraumeni syndrome (LFS) (Vahteristo P et al. Cancer Research. 2001 Aug;61:5718-5722; Pinto C et al. Fam. Cancer 2009 May;8:383-90; Melhem-Bertrandt A et al. Cancer. 2012 Feb;118(4):908-13; Mitchell G et al. PLoS One. 2013 Jul;8(7):e69026; Villani A et al. Lancet Oncol. 2016 Sep;17:1295-305; Saya S et al. Fam Cancer. 2017 Jul;16(3):433-440). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Jun 24, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000260299.13
First in ClinVar: Jan 31, 2016 Last updated: Mar 07, 2026 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Arg196*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is present in population databases (rs397516435, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 7978053, 11479205, 15381368, 19468865, 21552135, 23894400). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 43589). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Mar 30, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060186.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Comment:
show
The p.Arg196X variant in TP53 has been reported in >10 individuals with Li-Fraum eni syndrome, with a de novo occurrence in at least 1 individual, and segregated with disease in 1 affected relative from 1 family (Grayson 1994, Vahteristo 200 1, Bendig 2004, Trkova 2007, Pinto 2009, Masciari 2011, Mitchell 2013, Meric-Ber nstam 2016, Villani 2016, LMM data). It has also been identified in 1/111706 Eu ropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs397516435); however this frequency is low enough to be consistent with the frequency of Li-Fraumeni syndrome in the general population. This nonsense variant leads to a premature termination codon at position 196, w hich is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TP53 gene is an established disease mechanism in individuals wi th Li-Fraumeni syndrome. In summary, this variant meets criteria to be classifie d as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manner. ACMG/A MP criteria applied: PVS1, PM2, PM6. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Oct 10, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134872.3
First in ClinVar: Jan 04, 2020 Last updated: Jan 01, 2022 |
Comment:
show
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Nov 03, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011369.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
|
|
|
Pathogenic
(Feb 15, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome 1 |
Myriad Genetics, Inc.
Accession: SCV004932444.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
show
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Pathogenic
(Oct 18, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome |
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
Accession: SCV007449428.1
First in ClinVar: Feb 15, 2026 Last updated: Feb 15, 2026 |
Comment:
show
This variant is predicted to result in loss of function through nonsense-mediated decay of the encoded transcript or premature truncation of the encoded protein in a gene in which loss of function is a known mechanism of disease (ACMG/AMP: PVS1). This variant has been reported to occur de novo in an affected individual in the literature with parental identity confirmed (ACMG/AMP: PS2; PMID:15381368). This variant has been reported at an elevated frequency in affected individuals/in multiple affected individuals in the literature (ACMG/AMP: PS4; PMIDs:7978053, 11479205, 15381368, 19468865, 23580068, 23894400, 30709875). (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(May 10, 2017)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605426.2
First in ClinVar: Sep 30, 2017 Last updated: Feb 17, 2019 |
Comment:
show
The TP53 c.586C>T, p.Arg196Ter variant (rs397516435) has been reported in multiple individuals diagnosed with Li-Fraumeni syndrome (Bendig 2004, Grayson 1994, Vahteristo 2001, Villani 2016). It is observed in the Genome Aggregation Database general population database at a frequency of 0.00041 percent. The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Bendig I et al. Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. Cancer Genet Cytogenet. 2004; 154(1):22-6. Grayson G et al. Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma. Am J Pediatr Hematol Oncol. 1994; 16(4):341-7. Vahteristo P et al. p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Cancer Res. 2001; 61(15):5718-22. Villani A et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016; 17(9):1295-305. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(-)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf
Accession: SCV001482285.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
Observation 1
Collection method: research
Allele origin: de novo
Affected status: yes
Test name: Whole-Exome sequencing
Zygosity: 1 Single Heterozygote
Family history: no
Platform type: Next Generation Sequencing
|
|
|
Pathogenic
(Dec 08, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Color Diagnostics, LLC DBA Color Health
Accession: SCV001351214.2
First in ClinVar: Jun 22, 2020 Last updated: Jun 19, 2021 |
Comment:
show
This variant changes 1 nucleotide in exon 6 of the TP53 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with classic Li-Fraumeni syndrome (PMID: 11479205, 19468865), suspected Li-Fraumeni syndrome (PMID: 28573494), childhood adrenal cortical carcinoma (PMID: 7978053) and adult-onset sarcoma (PMID 23894400). This variant has also been observed de novo in an individual affected with rhabdomyosarcoma (PMID: 15381368) This variant has been identified in 1/251474 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Platform type: NGS
|
|
|
Pathogenic
(Jun 18, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Genome-Nilou Lab
Accession: SCV002582485.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Pathogenic
(Jun 18, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome 1 |
Genome-Nilou Lab
Accession: SCV002583146.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Pathogenic
(Nov 09, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
GeneDx
Accession: SCV000490858.3
First in ClinVar: Jan 09, 2017 Last updated: May 06, 2023 |
Comment:
show
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: decreased DNA binding and transactivation of p53 targets, loss of growth suppression activity (Malcikova 2010, Kotler 2018); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25757876, 10519380, 24696321, 22187033, 26787237, 28573494, 32504368, 33840814, 29922827, 34282142, 31721094, 17567834, 21761402, 21552135, 23894400, 20128691, 20805372, 25617798, 26425688, 25773284, 25412846, 11479205, 15381368, 19468865, 23580068, 18555592, 8080050, 10226610, 10567903, 12124823, 16322298, 27226433, 28091804, 27501770, 28177947, 29076966, 29979965, 29489754, 30709875, 30268473, 28991257, 30720243, 30730459, 7978053, 31105275, 30982232, 32817165, 31958074, 32368696, 33084842, 33674644, 34863587, 35974385, 35441217, 35418818, 25525159) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Jan 11, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Adrenocortical carcinoma, hereditary |
Baylor Genetics
Accession: SCV004204262.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Pathogenic
(Oct 23, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided
(Unknown mechanism)
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447028.2
First in ClinVar: Nov 28, 2020 Last updated: Apr 13, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Sex: female
|
|
|
Pathogenic
(Aug 16, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome 1 |
Molecular Genetics and NGS Laboratory, Hospital Fundacion Valle Del Lili
Accession: SCV005200616.2
First in ClinVar: Sep 08, 2024 Last updated: Apr 13, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Age: 30-39 years
Sex: female
Ethnicity/Population group: Latin
Geographic origin: Colombia
|
|
|
Pathogenic
(May 27, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast
Li-Fraumeni syndrome 1
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. |
Department of Pathology and Laboratory Medicine, Sinai Health System
Accession: SCV005918341.1
First in ClinVar: Apr 28, 2025 Last updated: Apr 28, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(-)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Li-Fraumeni syndrome 1 |
Genesis Genomics
Accession: SCV007580128.1
First in ClinVar: May 03, 2026 Last updated: May 03, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Clinical Features:
Breast cancer (present)
|
|
|
Pathogenic
(Oct 01, 2024)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
TP53-related disorder
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV005419149.1
First in ClinVar: Dec 07, 2024 Last updated: Dec 07, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Dec 01, 2018)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Ovarian neoplasm |
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923897.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
Observation 1
Collection method: research
Allele origin: somatic
Affected status: yes
Platform type: next-gen sequencing
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Study: VKGL Data-share Consensus
Accession: SCV001905932.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Study: VKGL Data-share Consensus
Accession: SCV001957804.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Mar 19, 2021)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Not specified
No history of cancer or disease
(more...)
|
University Health Network, Princess Margaret Cancer Centre
Accession: SCV001738479.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021 |
Observation 1
Collection method: clinical testing
Allele origin: somatic
Affected status: no
Secondary finding: yes
|
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Arg196*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is present in population databases (rs397516435, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 7978053, 11479205, 15381368, 19468865, 21552135, 23894400). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 43589). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Arg196X variant in TP53 has been reported in >10 individuals with Li-Fraum eni syndrome, with a de novo occurrence in at least 1 individual, and segregated with disease in 1 affected relative from 1 family (Grayson 1994, Vahteristo 200 1, Bendig 2004, Trkova 2007, Pinto 2009, Masciari 2011, Mitchell 2013, Meric-Ber nstam 2016, Villani 2016, LMM data). It has also been identified in 1/111706 Eu ropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs397516435); however this frequency is low enough to be consistent with the frequency of Li-Fraumeni syndrome in the general population. This nonsense variant leads to a premature termination codon at position 196, w hich is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TP53 gene is an established disease mechanism in individuals wi th Li-Fraumeni syndrome. In summary, this variant meets criteria to be classifie d as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manner. ACMG/A MP criteria applied: PVS1, PM2, PM6.
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Comment:
Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in spindle cell sarcoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Information in the literature supports potential biologic effect of variant (PMID: 27759562). 3) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 31276706, 34282771, 35705560, 35705558).
Comment:
This variant is predicted to result in loss of function through nonsense-mediated decay of the encoded transcript or premature truncation of the encoded protein in a gene in which loss of function is a known mechanism of disease (ACMG/AMP: PVS1). This variant has been reported to occur de novo in an affected individual in the literature with parental identity confirmed (ACMG/AMP: PS2; PMID:15381368). This variant has been reported at an elevated frequency in affected individuals/in multiple affected individuals in the literature (ACMG/AMP: PS4; PMIDs:7978053, 11479205, 15381368, 19468865, 23580068, 23894400, 30709875).
Comment:
The TP53 c.586C>T, p.Arg196Ter variant (rs397516435) has been reported in multiple individuals diagnosed with Li-Fraumeni syndrome (Bendig 2004, Grayson 1994, Vahteristo 2001, Villani 2016). It is observed in the Genome Aggregation Database general population database at a frequency of 0.00041 percent. The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Bendig I et al. Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. Cancer Genet Cytogenet. 2004; 154(1):22-6. Grayson G et al. Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma. Am J Pediatr Hematol Oncol. 1994; 16(4):341-7. Vahteristo P et al. p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Cancer Res. 2001; 61(15):5718-22. Villani A et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016; 17(9):1295-305.
Comment:
This variant changes 1 nucleotide in exon 6 of the TP53 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with classic Li-Fraumeni syndrome (PMID: 11479205, 19468865), suspected Li-Fraumeni syndrome (PMID: 28573494), childhood adrenal cortical carcinoma (PMID: 7978053) and adult-onset sarcoma (PMID 23894400). This variant has also been observed de novo in an individual affected with rhabdomyosarcoma (PMID: 15381368) This variant has been identified in 1/251474 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: decreased DNA binding and transactivation of p53 targets, loss of growth suppression activity (Malcikova 2010, Kotler 2018); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25757876, 10519380, 24696321, 22187033, 26787237, 28573494, 32504368, 33840814, 29922827, 34282142, 31721094, 17567834, 21761402, 21552135, 23894400, 20128691, 20805372, 25617798, 26425688, 25773284, 25412846, 11479205, 15381368, 19468865, 23580068, 18555592, 8080050, 10226610, 10567903, 12124823, 16322298, 27226433, 28091804, 27501770, 28177947, 29076966, 29979965, 29489754, 30709875, 30268473, 28991257, 30720243, 30730459, 7978053, 31105275, 30982232, 32817165, 31958074, 32368696, 33084842, 33674644, 34863587, 35974385, 35441217, 35418818, 25525159)
Comment on condition
No history of cancer or disease reported in this indivudal
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants. | Fortuno C | Human mutation | 2021 | PMID: 33300245 |
| Hematologic malignancies and Li-Fraumeni syndrome. | Swaminathan M | Cold Spring Harbor molecular case studies | 2019 | PMID: 30709875 |
| The landscape of genomic alterations across childhood cancers. | Gröbner SN | Nature | 2018 | PMID: 29489754 |
| A novel TP53 germline inframe deletion identified in a Spanish series of Li-fraumeni syndrome suspected families. | Llovet P | Familial cancer | 2017 | PMID: 28573494 |
| Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls. | Saya S | Familial cancer | 2017 | PMID: 28091804 |
| Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. | Villani A | The Lancet. Oncology | 2016 | PMID: 27501770 |
| Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol. | Meric-Bernstam F | Annals of oncology : official journal of the European Society for Medical Oncology | 2016 | PMID: 26787237 |
| Tumor genome analysis includes germline genome: are we ready for surprises? | Catenacci DV | International journal of cancer | 2015 | PMID: 25123297 |
| High frequency of germline TP53 mutations in a prospective adult-onset sarcoma cohort. | Mitchell G | PloS one | 2013 | PMID: 23894400 |
| Prevalence of germline TP53 mutations in HER2+ breast cancer patients. | Rath MG | Breast cancer research and treatment | 2013 | PMID: 23580068 |
| 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 |
| 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 |
| 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 |
| TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset. | Pinto C | Familial cancer | 2009 | PMID: 19468865 |
| Telomere length in peripheral blood cells of germline TP53 mutation carriers is shorter than that of normal individuals of corresponding age. | Trkova M | Cancer | 2007 | PMID: 17567834 |
| Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. | Bendig I | Cancer genetics and cytogenetics | 2004 | PMID: 15381368 |
| p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. | Vahteristo P | Cancer research | 2001 | PMID: 11479205 |
| Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma. | Grayson GH | The American journal of pediatric hematology/oncology | 1994 | PMID: 7978053 |
| click to load more citations click to collapse | ||||
Conditions - Somatic
| Tumor type
Help
The tumor type for this variant-condition (RCV) record in ClinVar. |
Clinical impact (# of submissions)
Help
The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Oncogenicity
Help
The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
Variation/condition record
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
|---|---|---|---|---|
|
Oncogenic
criteria provided, single submitter
|
Dec 29, 2025 | RCV006273074.1 | ||
|
Tier I (Strong)
- diagnostic
- supports diagnosis
(1)
|
Jan 16, 2025 | RCV006253728.1 |
Submissions - Somatic
|
Clinical impact
Help
The submitted somatic clinical impact for each SCV record. (Last evaluated) |
Review Status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Tumor type
Help
The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Expand all rows
Help
This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|
|
Tier I (Strong)
- Diagnostic
-
supports diagnosis (Jan 16, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Spindle cell sarcoma |
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
Accession: SCV007105583.1
First In ClinVar: Nov 22, 2025 Last updated: Nov 22, 2025 |
Comment:
show
Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in spindle cell sarcoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Information in the literature supports potential biologic effect of variant (PMID: 27759562). 3) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 31276706, 34282771, 35705560, 35705558). (less)
Observation: 1
Collection method: clinical testing
Allele origin: somatic
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: somatic
Affected status: yes
|
|
|
Oncogenicity
Help
The submitted oncogenicity classification for each SCV record. (Last evaluated) |
Review Status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Tumor type
Help
The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Expand all rows
Help
This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|
|
Oncogenic
(Dec 29, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Neoplasm |
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV007129871.1
First In ClinVar: Jan 03, 2026 Last updated: Jan 03, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: somatic
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: somatic
Affected status: yes
|
|
Comment:
The p.R196* pathogenic mutation (also known as c.586C>T), located in coding exon 5 of the TP53 gene, results from a C to T substitution at nucleotide position 586. This changes the amino acid from an arginine to a stop codon within coding exon 5. This mutation has been reported in a number of individuals with early onset or multiple cancers and in some families who meet either classic diagnostic criteria or Chompret criteria for Li-Fraumeni syndrome (LFS) (Vahteristo P et al. Cancer Research. 2001 Aug;61:5718-5722; Pinto C et al. Fam. Cancer 2009 May;8:383-90; Melhem-Bertrandt A et al. Cancer. 2012 Feb;118(4):908-13; Mitchell G et al. PLoS One. 2013 Jul;8(7):e69026; Villani A et al. Lancet Oncol. 2016 Sep;17:1295-305; Saya S et al. Fam Cancer. 2017 Jul;16(3):433-440). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
This sequence change creates a premature translational stop signal (p.Arg196*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is present in population databases (rs397516435, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 7978053, 11479205, 15381368, 19468865, 21552135, 23894400). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 43589). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Arg196X variant in TP53 has been reported in >10 individuals with Li-Fraum eni syndrome, with a de novo occurrence in at least 1 individual, and segregated with disease in 1 affected relative from 1 family (Grayson 1994, Vahteristo 200 1, Bendig 2004, Trkova 2007, Pinto 2009, Masciari 2011, Mitchell 2013, Meric-Ber nstam 2016, Villani 2016, LMM data). It has also been identified in 1/111706 Eu ropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs397516435); however this frequency is low enough to be consistent with the frequency of Li-Fraumeni syndrome in the general population. This nonsense variant leads to a premature termination codon at position 196, w hich is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TP53 gene is an established disease mechanism in individuals wi th Li-Fraumeni syndrome. In summary, this variant meets criteria to be classifie d as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manner. ACMG/A MP criteria applied: PVS1, PM2, PM6.
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Comment:
Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in spindle cell sarcoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Information in the literature supports potential biologic effect of variant (PMID: 27759562). 3) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 31276706, 34282771, 35705560, 35705558).
Comment:
This variant is predicted to result in loss of function through nonsense-mediated decay of the encoded transcript or premature truncation of the encoded protein in a gene in which loss of function is a known mechanism of disease (ACMG/AMP: PVS1). This variant has been reported to occur de novo in an affected individual in the literature with parental identity confirmed (ACMG/AMP: PS2; PMID:15381368). This variant has been reported at an elevated frequency in affected individuals/in multiple affected individuals in the literature (ACMG/AMP: PS4; PMIDs:7978053, 11479205, 15381368, 19468865, 23580068, 23894400, 30709875).
Comment:
The TP53 c.586C>T, p.Arg196Ter variant (rs397516435) has been reported in multiple individuals diagnosed with Li-Fraumeni syndrome (Bendig 2004, Grayson 1994, Vahteristo 2001, Villani 2016). It is observed in the Genome Aggregation Database general population database at a frequency of 0.00041 percent. The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Bendig I et al. Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin. Cancer Genet Cytogenet. 2004; 154(1):22-6. Grayson G et al. Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma. Am J Pediatr Hematol Oncol. 1994; 16(4):341-7. Vahteristo P et al. p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Cancer Res. 2001; 61(15):5718-22. Villani A et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016; 17(9):1295-305.
Comment:
This variant changes 1 nucleotide in exon 6 of the TP53 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with classic Li-Fraumeni syndrome (PMID: 11479205, 19468865), suspected Li-Fraumeni syndrome (PMID: 28573494), childhood adrenal cortical carcinoma (PMID: 7978053) and adult-onset sarcoma (PMID 23894400). This variant has also been observed de novo in an individual affected with rhabdomyosarcoma (PMID: 15381368) This variant has been identified in 1/251474 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: decreased DNA binding and transactivation of p53 targets, loss of growth suppression activity (Malcikova 2010, Kotler 2018); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25757876, 10519380, 24696321, 22187033, 26787237, 28573494, 32504368, 33840814, 29922827, 34282142, 31721094, 17567834, 21761402, 21552135, 23894400, 20128691, 20805372, 25617798, 26425688, 25773284, 25412846, 11479205, 15381368, 19468865, 23580068, 18555592, 8080050, 10226610, 10567903, 12124823, 16322298, 27226433, 28091804, 27501770, 28177947, 29076966, 29979965, 29489754, 30709875, 30268473, 28991257, 30720243, 30730459, 7978053, 31105275, 30982232, 32817165, 31958074, 32368696, 33084842, 33674644, 34863587, 35974385, 35441217, 35418818, 25525159)
Comment on condition
No history of cancer or disease reported in this indivudal
Citations for somatic classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets. | Nacev BA | Nature communications | 2022 | PMID: 35705560 |
| Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma. | Gounder MM | Nature communications | 2022 | PMID: 35705558 |
| TP53 Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials. | Nassif EF | Cancers | 2021 | PMID: 34282771 |
| TP53 in bone and soft tissue sarcomas. | Thoenen E | Pharmacology & therapeutics | 2019 | PMID: 31276706 |
| A quantitative model to predict pathogenicity of missense variants in the TP53 gene. | Fortuno C | Human mutation | 2019 | PMID: 30840781 |
| TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. | Shirole NH | eLife | 2016 | PMID: 27759562 |
Text-mined citations for rs397516435 ...
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 Jun 06, 2026
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.