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NM_000546.6(TP53):c.403T>A (p.Cys135Ser) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 22, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000814994.11

Allele description [Variation Report for NM_000546.6(TP53):c.403T>A (p.Cys135Ser)]

NM_000546.6(TP53):c.403T>A (p.Cys135Ser)

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.403T>A (p.Cys135Ser)
HGVS:
  • NC_000017.11:g.7675209A>T
  • NG_017013.2:g.17342T>A
  • NM_000546.6:c.403T>AMANE SELECT
  • NM_001126112.3:c.403T>A
  • NM_001126113.3:c.403T>A
  • NM_001126114.3:c.403T>A
  • NM_001126115.2:c.7T>A
  • NM_001126116.2:c.7T>A
  • NM_001126117.2:c.7T>A
  • NM_001126118.2:c.286T>A
  • NM_001276695.3:c.286T>A
  • NM_001276696.3:c.286T>A
  • NM_001276697.3:c.-75T>A
  • NM_001276698.3:c.-75T>A
  • NM_001276699.3:c.-75T>A
  • NM_001276760.3:c.286T>A
  • NM_001276761.3:c.286T>A
  • NP_000537.3:p.Cys135Ser
  • NP_000537.3:p.Cys135Ser
  • NP_001119584.1:p.Cys135Ser
  • NP_001119585.1:p.Cys135Ser
  • NP_001119586.1:p.Cys135Ser
  • NP_001119587.1:p.Cys3Ser
  • NP_001119588.1:p.Cys3Ser
  • NP_001119589.1:p.Cys3Ser
  • NP_001119590.1:p.Cys96Ser
  • NP_001263624.1:p.Cys96Ser
  • NP_001263625.1:p.Cys96Ser
  • NP_001263689.1:p.Cys96Ser
  • NP_001263690.1:p.Cys96Ser
  • LRG_321t1:c.403T>A
  • LRG_321:g.17342T>A
  • LRG_321p1:p.Cys135Ser
  • NC_000017.10:g.7578527A>T
  • NM_000546.5:c.403T>A
Protein change:
C135S
Links:
dbSNP: rs1057519975
NCBI 1000 Genomes Browser:
rs1057519975
Molecular consequence:
  • NM_001276697.3:c.-75T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276698.3:c.-75T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276699.3:c.-75T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.6:c.403T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.403T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.403T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.403T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.7T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.7T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.7T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.286T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.286T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.286T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.286T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.286T>A - 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
SCV000955434Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 22, 2020)
germlineclinical testing

PubMed (8)
[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

Mutant p53 in bone marrow stromal cells increases VEGF expression and supports leukemia cell growth.

Narendran A, Ganjavi H, Morson N, Connor A, Barlow JW, Keystone E, Malkin D, Freedman MH.

Exp Hematol. 2003 Aug;31(8):693-701.

PubMed [citation]
PMID:
12901974
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000955434.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 135 of the TP53 protein (p.Cys135Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376562). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change impairs the transcriptional transactivation activity of the TP53 protein and results in the lost ability to inhibit cell proliferation in yeast and cell lines (PMID: 12826609, 12901974, 1918170, 7750099, 24940547, 12034820, 19681600).

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

Last Updated: Dec 28, 2024