ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.807C>G (p.Ser269Arg)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000546.6(TP53):c.807C>G (p.Ser269Arg)
Variation ID: 2113149 Accession: VCV002113149.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7673813 (GRCh38) [ NCBI UCSC ] 17: 7577131 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 8, 2023 Feb 20, 2024 Jul 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000546.6:c.807C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Ser269Arg missense NM_001126112.3:c.807C>G NP_001119584.1:p.Ser269Arg missense NM_001126113.3:c.807C>G NP_001119585.1:p.Ser269Arg missense NM_001126114.3:c.807C>G NP_001119586.1:p.Ser269Arg missense NM_001126115.2:c.411C>G NP_001119587.1:p.Ser137Arg missense NM_001126116.2:c.411C>G NP_001119588.1:p.Ser137Arg missense NM_001126117.2:c.411C>G NP_001119589.1:p.Ser137Arg missense NM_001126118.2:c.690C>G NP_001119590.1:p.Ser230Arg missense NM_001276695.3:c.690C>G NP_001263624.1:p.Ser230Arg missense NM_001276696.3:c.690C>G NP_001263625.1:p.Ser230Arg missense NM_001276697.3:c.330C>G NP_001263626.1:p.Ser110Arg missense NM_001276698.3:c.330C>G NP_001263627.1:p.Ser110Arg missense NM_001276699.3:c.330C>G NP_001263628.1:p.Ser110Arg missense NM_001276760.3:c.690C>G NP_001263689.1:p.Ser230Arg missense NM_001276761.3:c.690C>G NP_001263690.1:p.Ser230Arg missense NM_001407262.1:c.807C>G NP_001394191.1:p.Ser269Arg missense NM_001407263.1:c.690C>G NP_001394192.1:p.Ser230Arg missense NM_001407264.1:c.807C>G NP_001394193.1:p.Ser269Arg missense NM_001407265.1:c.690C>G NP_001394194.1:p.Ser230Arg missense NM_001407266.1:c.807C>G NP_001394195.1:p.Ser269Arg missense NM_001407267.1:c.690C>G NP_001394196.1:p.Ser230Arg missense NM_001407268.1:c.807C>G NP_001394197.1:p.Ser269Arg missense NM_001407269.1:c.690C>G NP_001394198.1:p.Ser230Arg missense NM_001407270.1:c.807C>G NP_001394199.1:p.Ser269Arg missense NM_001407271.1:c.690C>G NP_001394200.1:p.Ser230Arg missense NR_176326.1:n.836C>G NC_000017.11:g.7673813G>C NC_000017.10:g.7577131G>C NG_017013.2:g.18738C>G LRG_321:g.18738C>G LRG_321t1:c.807C>G LRG_321p1:p.Ser269Arg LRG_321t2:c.807C>G LRG_321:p.Ser269Arg LRG_321t3:c.807C>G LRG_321p3:p.Ser269Arg LRG_321t4:c.807C>G LRG_321p4:p.Ser269Arg LRG_321t5:c.411C>G LRG_321p5:p.Ser137Arg LRG_321t6:c.411C>G LRG_321p6:p.Ser137Arg LRG_321t7:c.411C>G LRG_321p7:p.Ser137Arg LRG_321t8:c.690C>G LRG_321p8:p.Ser230Arg - Protein change
- S110R, S137R, S230R, S269R
- Other names
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- Canonical SPDI
- NC_000017.11:7673812:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3323 | 3421 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Dec 9, 2022 | RCV003038628.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 28, 2023 | RCV003477033.1 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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. |
More information
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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. |
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Uncertain significance
(Jul 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221375.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
This variant has not been reported as a germline variant in individuals with TP53-related conditions in the published literature. In vitro studies have shown that … (more)
This variant has not been reported as a germline variant in individuals with TP53-related conditions in the published literature. In vitro studies have shown that this variant disrupts cell cycle arrest function of p53 protein but retains the apoptotic activity (PMID: 12456286 (2002)). This variant also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Additional analysis using software algorithms for the prediction of the effect of nucleotide changes on TP53 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain significance
(Dec 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003324448.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 269 of the TP53 protein (p.Ser269Arg). (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genetic alterations of triple negative breast cancer (TNBC) in women from Northeastern Mexico. | Uscanga-Perales GI | Oncology letters | 2019 | PMID: 30867801 |
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 |
Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer. | Pang JB | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 2017 | PMID: 28338653 |
In vitro radiosensitization by pentoxifylline does not depend on p53 status. | Akudugu JM | International journal of radiation biology | 2013 | PMID: 23363223 |
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 |
Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants. | Binder A | International journal of radiation biology | 2002 | PMID: 12456286 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 29, 2024
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.