NM_000546.6(TP53):c.380C>T (p.Ser127Phe) AND Li-Fraumeni syndrome

Clinical significance:Likely pathogenic (Last evaluated: Feb 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000633384.4

Allele description [Variation Report for NM_000546.6(TP53):c.380C>T (p.Ser127Phe)]

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

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.380C>T (p.Ser127Phe)
Other names:
p.S127F:TCC>TTC
HGVS:
  • NC_000017.11:g.7675232G>A
  • NG_017013.2:g.17319C>T
  • NM_000546.5:c.380C>T
  • NM_000546.6:c.380C>TMANE SELECT
  • NM_001126112.2:c.380C>T
  • NM_001126113.2:c.380C>T
  • NM_001126114.2:c.380C>T
  • NM_001126115.1:c.-17C>T
  • NM_001126116.1:c.-17C>T
  • NM_001126117.1:c.-17C>T
  • NM_001126118.1:c.263C>T
  • NM_001276695.2:c.263C>T
  • NM_001276696.2:c.263C>T
  • NM_001276697.2:c.-98C>T
  • NM_001276698.2:c.-98C>T
  • NM_001276699.2:c.-98C>T
  • NM_001276760.2:c.263C>T
  • NM_001276761.2:c.263C>T
  • NP_000537.3:p.Ser127Phe
  • NP_000537.3:p.Ser127Phe
  • NP_001119584.1:p.Ser127Phe
  • NP_001119585.1:p.Ser127Phe
  • NP_001119586.1:p.Ser127Phe
  • NP_001119590.1:p.Ser88Phe
  • NP_001263624.1:p.Ser88Phe
  • NP_001263625.1:p.Ser88Phe
  • NP_001263689.1:p.Ser88Phe
  • NP_001263690.1:p.Ser88Phe
  • LRG_321t1:c.380C>T
  • LRG_321t2:c.380C>T
  • LRG_321t3:c.380C>T
  • LRG_321t4:c.380C>T
  • LRG_321t5:c.-17C>T
  • LRG_321t6:c.-17C>T
  • LRG_321t7:c.-17C>T
  • LRG_321t8:c.263C>T
  • LRG_321:g.17319C>T
  • LRG_321:p.Ser127Phe
  • LRG_321p1:p.Ser127Phe
  • LRG_321p3:p.Ser127Phe
  • LRG_321p4:p.Ser127Phe
  • LRG_321p8:p.Ser88Phe
  • NC_000017.10:g.7578550G>A
  • NM_000546.4:c.380C>T
  • P04637:p.Ser127Phe
Protein change:
S127F
Links:
UniProtKB: P04637#VAR_005867; dbSNP: rs730881999
NCBI 1000 Genomes Browser:
rs730881999
Molecular consequence:
  • NM_001126115.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126116.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126117.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276697.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276698.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276699.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.5:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000754606Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 20, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]
PMID:
12826609
PMCID:
PMC166245

Assessment of the transcriptional activity of p53 improves the prediction of recurrence in superficial transitional cell carcinoma of the bladder.

Dekairelle AF, Tombal B, Cosyns JP, Gala JL.

Clin Cancer Res. 2005 Jul 1;11(13):4724-32.

PubMed [citation]
PMID:
16000567
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000754606.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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 large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Li-Fraumeni syndrome (LFS)-associated tumors in a family (external communication). ClinVar contains an entry for this variant (Variation ID: 182928). This variant has been reported to affect TP53 protein function (PMID: 12826609, 16000567, 16322298, 29979965). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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