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NM_000546.5(TP53):c.917G>A (p.Arg306Gln)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Feb 15, 2020
Accession:
VCV000458574.9
Variation ID:
458574
Description:
single nucleotide variant
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NM_000546.5(TP53):c.917G>A (p.Arg306Gln)

Allele ID
469117
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7673703 (GRCh38) GRCh38 UCSC
17: 7577021 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.11:g.7673703C>T
NC_000017.10:g.7577021C>T
NM_000546.5:c.917G>A NP_000537.3:p.Arg306Gln missense
... more HGVS
Protein change
R267Q, R306Q, R174Q, R147Q
Other names
-
Canonical SPDI
NC_000017.11:7673702:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA287486566
dbSNP: rs1048095040
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Aug 21, 2019 RCV000561902.4
Uncertain significance 1 criteria provided, single submitter Jun 13, 2017 RCV000664300.1
Uncertain significance 1 criteria provided, single submitter Jul 8, 2019 RCV000986056.1
Uncertain significance 1 criteria provided, single submitter May 28, 2019 RCV000989706.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Feb 15, 2020 RCV000527123.5
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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
(Jun 13, 2017)
criteria provided, single submitter
Method: research
Familial cancer of breast
(Autosomal dominant inheritance)
Allele origin: germline
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000788229.1
Submitted: (Mar 09, 2018)
Evidence details
Publications
PubMed (3)
Comment:
The TP53 variant designated as NM_000546.5:c.917G>A (p.Arg306Gln) is classified as variant of uncertain significance in the context of famiial breast cancer. Loss of heterozygosity was … (more)
Likely benign
(Mar 28, 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: SCV000788228.2
Submitted: (Nov 05, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The TP53 variant designated as NM_000546.5:c.917G>A (p.Arg306Gln) is classified as likely benign in the context of Li-Fraumeni syndrome. Cosegregation analysis of one observed family was … (more)
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Squamous cell carcinoma of the head and neck
Allele origin: unknown
Mendelics
Accession: SCV001140245.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(Jul 08, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134880.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (3)
Uncertain significance
(Aug 21, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000686782.3
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with glutamine at codon 306 of the TP53 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact … (more)
Evidence details
Uncertain significance
(Dec 20, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000664396.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.R306Q variant (also known as c.917G>A), located in coding exon 7 of the TP53 gene, results from a G to A substitution at nucleotide … (more)
Uncertain significance
(Feb 15, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV000629886.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces arginine with glutamine at codon 306 of the TP53 protein (p.Arg306Gln). The arginine residue is highly conserved and there is a … (more)

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
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
Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis. de Andrade KC Human mutation 2019 PMID: 30352134
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Recurrent TP53 missense mutation in cancer patients of Arab descent. Zick A Familial cancer 2017 PMID: 27866339
Germline TP53 mutational spectrum in French Canadians with breast cancer. Arcand SL BMC medical genetics 2015 PMID: 25925845
Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations. Deb S British journal of cancer 2014 PMID: 25490678
Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil. Giacomazzi J PloS one 2014 PMID: 24936644
Beyond BRCA1 and BRCA2 wild-type breast and/or ovarian cancer families: germline mutations in TP53 and PTEN. Blanco A Clinical genetics 2010 PMID: 19930417
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

Text-mined citations for rs1048095040...

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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 Apr 08, 2021