Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000546.6(TP53):c.380C>T (p.Ser127Phe)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: May 19, 2021)
Last evaluated:
Feb 20, 2020
Accession:
VCV000182928.8
Variation ID:
182928
Description:
single nucleotide variant
Help

NM_000546.6(TP53):c.380C>T (p.Ser127Phe)

Allele ID
181015
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7675232 (GRCh38) GRCh38 UCSC
17: 7578550 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7578550G>A
NC_000017.11:g.7675232G>A
NM_000546.6:c.380C>T MANE Select NP_000537.3:p.Ser127Phe missense
... more HGVS
Protein change
S127F, S88F
Other names
p.S127F:TCC>TTC
Canonical SPDI
NC_000017.11:7675231:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA000148
UniProtKB: P04637#VAR_005867
dbSNP: rs730881999
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Jun 29, 2018 RCV000161024.3
Uncertain significance 1 criteria provided, single submitter Nov 22, 2016 RCV000606528.1
Likely pathogenic 1 criteria provided, single submitter Feb 20, 2020 RCV000633384.4
Pathogenic/Likely pathogenic 2 no assertion criteria provided Mar 19, 2021 RCV000785332.2
Help
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
2189 2252

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jun 29, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000211743.13
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted TP53 c.380C>T at the cDNA level, p.Ser127Phe (S127F) at the protein level, and results in the change of a Serine to … (more)
Uncertain significance
(Nov 22, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000712629.2
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The p.Ser127Phe variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. Computational predicti on tools and … (more)
Likely pathogenic
(Feb 20, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV000754606.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces serine with phenylalanine at codon 127 of the TP53 protein (p.Ser127Phe). The serine residue is highly conserved and there is a … (more)
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: SCV000923900.1
Submitted: (Feb 22, 2019)
Evidence details
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: SCV001738483.1
Submitted: (May 19, 2021)
Evidence details

Functional evidence

Help
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

Help
Title Author Journal Year Link
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. Kotler E Molecular cell 2018 PMID: 29979965
Clinical relevance of dominant-negative p73 isoforms for responsiveness to chemotherapy and survival in ovarian cancer: evidence for a crucial p53-p73 cross-talk in vivo. Concin N Clinical cancer research : an official journal of the American Association for Cancer Research 2005 PMID: 16322298
Assessment of the transcriptional activity of p53 improves the prediction of recurrence in superficial transitional cell carcinoma of the bladder. Dekairelle AF Clinical cancer research : an official journal of the American Association for Cancer Research 2005 PMID: 16000567
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 rs730881999...

Help
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 Jul 07, 2021