ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.1014C>T (p.Phe338=)
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.1014C>T (p.Phe338=)
Variation ID: 182952 Accession: VCV000182952.57
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7670695 (GRCh38) [ NCBI UCSC ] 17: 7574013 (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 May 29, 2016 May 12, 2024 Feb 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000546.6:c.1014C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Phe338= synonymous NM_001126112.3:c.1014C>T NP_001119584.1:p.Phe338= synonymous NM_001126113.3:c.*33C>T 3 prime UTR NM_001126114.3:c.*121C>T 3 prime UTR NM_001126115.2:c.618C>T NP_001119587.1:p.Phe206= synonymous NM_001126116.2:c.*121C>T 3 prime UTR NM_001126117.2:c.*33C>T 3 prime UTR NM_001126118.2:c.897C>T NP_001119590.1:p.Phe299= synonymous NM_001276695.3:c.*33C>T 3 prime UTR NM_001276696.3:c.*121C>T 3 prime UTR NM_001276697.3:c.537C>T NP_001263626.1:p.Phe179= synonymous NM_001276698.3:c.*121C>T 3 prime UTR NM_001276699.3:c.*33C>T 3 prime UTR NM_001276760.3:c.897C>T NP_001263689.1:p.Phe299= synonymous NM_001276761.3:c.897C>T NP_001263690.1:p.Phe299= synonymous NC_000017.11:g.7670695G>A NC_000017.10:g.7574013G>A NG_017013.2:g.21856C>T LRG_321:g.21856C>T LRG_321t1:c.1014C>T LRG_321p1:p.Phe338= LRG_321t6:c.*121C>T - Protein change
- Other names
- p.F338F:TTC>TTT
- Canonical SPDI
- NC_000017.11:7670694:G:A
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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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0.00020 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00018
Trans-Omics for Precision Medicine (TOPMed) 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
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 | ||
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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. |
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TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3307 | 3402 |
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. |
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Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jun 18, 2022 | RCV000161054.10 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000213067.13 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2023 | RCV000590822.31 | |
Likely benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000989699.3 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV001127283.8 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 5, 2024 | RCV001084218.11 |
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. |
More information
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. |
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Likely benign
(Oct 29, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537467.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
|
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Likely benign
(May 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806230.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
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Likely benign
(Mar 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV003799832.2
First in ClinVar: Feb 13, 2023 Last updated: Mar 04, 2023 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015639.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
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Likely benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002760879.3
First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023 |
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Benign
(Mar 17, 2022)
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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: SCV000889879.4
First in ClinVar: Mar 17, 2018 Last updated: Jan 06, 2024 |
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Likely benign
(Feb 01, 2024)
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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: SCV000253304.12
First in ClinVar: Oct 11, 2015 Last updated: Feb 14, 2024 |
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Likely Benign
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004823729.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 72
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Benign
(Apr 25, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697423.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.1014C>T variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. 5/5 … (more)
Variant summary: The c.1014C>T variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. 5/5 splice-tools in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions are not confirmed by experimental studies. This variant is found in 26/117820 control chromosomes at a frequency of 0.0002207, which is about 6 times of the maximal expected frequency of a pathogenic allele (0.0000354), suggesting this variant is benign. In addition, multiple clinical laboratories classified this variant as benign/likely benign. Taken together, this variant was classified as benign. (less)
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Benign
(Jul 09, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000211784.10
First in ClinVar: Feb 24, 2015 Last updated: Feb 19, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Squamous cell carcinoma of the head and neck
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001140238.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Nov 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001286578.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Apr 20, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002530418.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
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Likely benign
(Jun 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002582776.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
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Likely benign
(Jun 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002582214.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
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Likely benign
(Jul 16, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000213005.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Jun 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001151189.22
First in ClinVar: Feb 03, 2020 Last updated: May 12, 2024 |
Comment:
TP53: BP4, BP7
Number of individuals with the variant: 5
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000692059.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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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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TP53 germline mutations in the context of families with hereditary breast and ovarian cancer: a clinical challenge. | Grill S | Archives of gynecology and obstetrics | 2021 | PMID: 33245408 |
TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients. | Kandioler D | EBioMedicine | 2015 | PMID: 26425688 |
Mutational landscape of aggressive cutaneous squamous cell carcinoma. | Pickering CR | Clinical cancer research : an official journal of the American Association for Cancer Research | 2014 | PMID: 25303977 |
TP53 mutations in human cancer: database reassessment and prospects for the next decade. | Leroy B | Human mutation | 2014 | PMID: 24665023 |
Synonymous mutations frequently act as driver mutations in human cancers. | Supek F | Cell | 2014 | PMID: 24630730 |
Different mutation profiles associated to P53 accumulation in colorectal cancer. | López I | Gene | 2012 | PMID: 22373952 |
Understanding the contribution of synonymous mutations to human disease. | Sauna ZE | Nature reviews. Genetics | 2011 | PMID: 21878961 |
Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect. | Nicholls CD | The Journal of biological chemistry | 2002 | PMID: 11805092 |
Mutations in the conserved regions of p53 are infrequent in betel-associated oral cancers from Papua New Guinea. | Thomas S | Cancer research | 1994 | PMID: 8012986 |
Text-mined citations for rs150293825 ...
HelpRecord last updated May 12, 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.