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NM_000546.6(TP53):c.527G>T (p.Cys176Phe) AND Li-Fraumeni syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 4, 2023
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:
RCV001244047.8

Allele description [Variation Report for NM_000546.6(TP53):c.527G>T (p.Cys176Phe)]

NM_000546.6(TP53):c.527G>T (p.Cys176Phe)

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.527G>T (p.Cys176Phe)
HGVS:
  • NC_000017.11:g.7675085C>A
  • NG_017013.2:g.17466G>T
  • NM_000546.6:c.527G>TMANE SELECT
  • NM_001126112.3:c.527G>T
  • NM_001126113.3:c.527G>T
  • NM_001126114.3:c.527G>T
  • NM_001126115.2:c.131G>T
  • NM_001126116.2:c.131G>T
  • NM_001126117.2:c.131G>T
  • NM_001126118.2:c.410G>T
  • NM_001276695.3:c.410G>T
  • NM_001276696.3:c.410G>T
  • NM_001276697.3:c.50G>T
  • NM_001276698.3:c.50G>T
  • NM_001276699.3:c.50G>T
  • NM_001276760.3:c.410G>T
  • NM_001276761.3:c.410G>T
  • NP_000537.3:p.Cys176Phe
  • NP_000537.3:p.Cys176Phe
  • NP_001119584.1:p.Cys176Phe
  • NP_001119585.1:p.Cys176Phe
  • NP_001119586.1:p.Cys176Phe
  • NP_001119587.1:p.Cys44Phe
  • NP_001119588.1:p.Cys44Phe
  • NP_001119589.1:p.Cys44Phe
  • NP_001119590.1:p.Cys137Phe
  • NP_001263624.1:p.Cys137Phe
  • NP_001263625.1:p.Cys137Phe
  • NP_001263626.1:p.Cys17Phe
  • NP_001263627.1:p.Cys17Phe
  • NP_001263628.1:p.Cys17Phe
  • NP_001263689.1:p.Cys137Phe
  • NP_001263690.1:p.Cys137Phe
  • LRG_321t1:c.527G>T
  • LRG_321:g.17466G>T
  • LRG_321p1:p.Cys176Phe
  • NC_000017.10:g.7578403C>A
  • NM_000546.4:c.527G>T
  • NM_000546.5:c.527G>T
Protein change:
C137F
Links:
dbSNP: rs786202962
NCBI 1000 Genomes Browser:
rs786202962
Molecular consequence:
  • NM_000546.6:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.131G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.131G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.131G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.50G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.50G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.50G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.410G>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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001417241Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 4, 2023) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Complex functions of mutant p53 alleles from human prostate cancer.

Shi XB, Nesslinger NJ, Deitch AD, Gumerlock PH, deVere White RW.

Prostate. 2002 Apr 1;51(1):59-72.

PubMed [citation]
PMID:
11920959

Inactive full-length p53 mutants lacking dominant wild-type p53 inhibition highlight loss of heterozygosity as an important aspect of p53 status in human cancers.

Dearth LR, Qian H, Wang T, Baroni TE, Zeng J, Chen SW, Yi SY, Brachmann RK.

Carcinogenesis. 2007 Feb;28(2):289-98. Epub 2006 Jul 21.

PubMed [citation]
PMID:
16861262
See all PubMed Citations (11)

Details of each submission

From Invitae, SCV001417241.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

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. Experimental studies have shown that this missense change affects TP53 function (PMID: 11920959, 12826609, 16861262, 18555592, 20407015, 22090360). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 376569). This missense change has been observed in individual(s) with Li-Fraumeni syndrome, pleural mesothelioma and acute myeloid leukemia (PMID: 26554828, 27622479). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 176 of the TP53 protein (p.Cys176Phe).

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

Last Updated: May 12, 2024