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NM_000546.6(TP53):c.747G>T

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(3);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Aug 13, 2021)
Last evaluated:
Mar 11, 2021
Accession:
VCV000012352.6
Variation ID:
12352
Description:
single nucleotide variant
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NM_000546.6(TP53):c.747G>T

Allele ID
27391
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7674216 (GRCh38) GRCh38 UCSC
17: 7577534 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7577534C>A
NC_000017.11:g.7674216C>A
NM_000546.6:c.747G>T MANE Select
... more HGVS
Protein change
R249S, R117S, R210S, R90S
Other names
-
Canonical SPDI
NC_000017.11:7674215:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA000392
UniProtKB: P04637#VAR_005986
OMIM: 191170.0006
dbSNP: rs28934571
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Sep 9, 2018 RCV000579519.2
Pathogenic 1 criteria provided, single submitter - RCV001270276.1
Pathogenic 1 criteria provided, single submitter Mar 11, 2021 RCV001562247.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations May 25, 2018 RCV000464372.2
Pathogenic 1 no assertion criteria provided May 2, 1992 RCV000013145.4
Pathogenic 1 no assertion criteria provided May 2, 1992 RCV000013146.4
Likely pathogenic 2 no assertion criteria provided Mar 19, 2021 RCV000785491.2
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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
2197 2260

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 10, 2016)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV000545320.2
Submitted: (Mar 14, 2017)
Evidence details
Comment:
This sequence change replaces arginine with serine at codon 249 of the TP53 protein (p.Arg249Ser). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Mar 11, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001784983.1
Submitted: (Aug 13, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect: non-functional transactivation, impaired growth suppression and apoptotic abilities, and exhibits a dominant negative effect (Chen 1996, Kato 2003, … (more)
Pathogenic
(May 25, 2018)
criteria provided, single submitter
Method: research
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Allele origin: germline
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000886463.1
Submitted: (Nov 05, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The TP53 variant designated as NM_000546.5:c.747G>T (p.Arg249Ser) is classified as pathogenic. This variant has not been reported in public population databases. Cosegregation analysis of one … (more)
Uncertain significance
(Sep 09, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000686767.2
Submitted: (Nov 06, 2018)
Evidence details
Pathogenic
(-)
criteria provided, single submitter
Method: case-control
Squamous cell carcinoma of the head and neck
Allele origin: somatic
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo
Accession: SCV001450493.1
Submitted: (Dec 08, 2020)
Evidence details
Publications
PubMed (1)
Pathogenic
(May 02, 1992)
no assertion criteria provided
Method: literature only
HEPATOCELLULAR CARCINOMA, SOMATIC
Allele origin: somatic
OMIM
Accession: SCV000033392.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
Pathogenic
(May 02, 1992)
no assertion criteria provided
Method: literature only
CERVICAL CANCER, SOMATIC
Allele origin: somatic
OMIM
Accession: SCV000033393.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Dec 01, 2018)
no assertion criteria provided
Method: research
Neoplasm of ovary
Allele origin: somatic
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne
Accession: SCV000924063.1
Submitted: (Feb 22, 2019)
Evidence details
Likely pathogenic
(Mar 19, 2021)
no assertion criteria provided
Method: clinical testing
Neoplasm of ovary
Allele origin: somatic
University Health Network,Princess Margaret Cancer Centre
Accession: SCV001738477.1
Submitted: (May 19, 2021)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
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
Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance. Tsai GJ Genetics in medicine : official journal of the American College of Medical Genetics 2019 PMID: 30374176
Clonal p53 mutation in primary cervical cancer: association with human-papillomavirus-negative tumours. Crook T Lancet (London, England) 1992 PMID: 1349102
Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Hsu IC Nature 1991 PMID: 1849234

Text-mined citations for rs28934571...

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These 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 Aug 17, 2021