NM_000546.6(TP53):c.760A>G (p.Ile254Val) AND Li-Fraumeni syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000477424.7

Allele description [Variation Report for NM_000546.6(TP53):c.760A>G (p.Ile254Val)]

NM_000546.6(TP53):c.760A>G (p.Ile254Val)

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.760A>G (p.Ile254Val)
Other names:
NM_000546.5(TP53):c.760A>G; p.Ile254Val
HGVS:
  • NC_000017.11:g.7674203T>C
  • NC_000017.11:g.7674203T>C
  • NG_017013.2:g.18348A>G
  • NM_000546.5:c.760A>G
  • NM_000546.6:c.760A>GMANE SELECT
  • NM_001126112.3:c.760A>G
  • NM_001126113.3:c.760A>G
  • NM_001126114.3:c.760A>G
  • NM_001126115.2:c.364A>G
  • NM_001126116.2:c.364A>G
  • NM_001126117.2:c.364A>G
  • NM_001126118.2:c.643A>G
  • NM_001276695.3:c.643A>G
  • NM_001276696.3:c.643A>G
  • NM_001276697.3:c.283A>G
  • NM_001276698.3:c.283A>G
  • NM_001276699.3:c.283A>G
  • NM_001276760.3:c.643A>G
  • NM_001276761.3:c.643A>G
  • NP_000537.3:p.Ile254Val
  • NP_000537.3:p.Ile254Val
  • NP_001119584.1:p.Ile254Val
  • NP_001119585.1:p.Ile254Val
  • NP_001119586.1:p.Ile254Val
  • NP_001119587.1:p.Ile122Val
  • NP_001119588.1:p.Ile122Val
  • NP_001119589.1:p.Ile122Val
  • NP_001119590.1:p.Ile215Val
  • NP_001263624.1:p.Ile215Val
  • NP_001263625.1:p.Ile215Val
  • NP_001263626.1:p.Ile95Val
  • NP_001263627.1:p.Ile95Val
  • NP_001263628.1:p.Ile95Val
  • NP_001263689.1:p.Ile215Val
  • NP_001263690.1:p.Ile215Val
  • LRG_321t1:c.760A>G
  • LRG_321:g.18348A>G
  • LRG_321p1:p.Ile254Val
  • NC_000017.10:g.7577521T>C
  • NC_000017.10:g.7577521T>C
  • NM_000546.4:c.760A>G
Protein change:
I122V
Links:
dbSNP: rs746601313
NCBI 1000 Genomes Browser:
rs746601313
Molecular consequence:
  • NM_000546.5:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.364A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.364A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.364A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.283A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.283A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.283A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.643A>G - 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
SCV000545356Invitaecriteria provided, single submitter
Uncertain significance
(Oct 30, 2020)
germlineclinical testing

PubMed (9)
[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

TP53 Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients.

Halvorsen AR, Silwal-Pandit L, Meza-Zepeda LA, Vodak D, Vu P, Sagerup C, Hovig E, Myklebost O, Børresen-Dale AL, Brustugun OT, Helland Å.

Front Genet. 2016;7:85. doi: 10.3389/fgene.2016.00085.

PubMed [citation]
PMID:
27242894
PMCID:
PMC4863128

Genetic testing and prevention of hereditary cancer at the MMCI--over 10 years of experience.

Foretova L, Petrakova K, Palacova M, Kalabova R, Svoboda M, Navratilova M, Schneiderova M, Bolcak K, Krejci E, Drazan L, Mikova M, Hazova J, Vasickova P, Machackova E.

Klin Onkol. 2010;23(6):388-400. Review.

PubMed [citation]
PMID:
21348412
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000545356.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces isoleucine with valine at codon 254 of the TP53 protein (p.Ile254Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs746601313, ExAC 0.001%). This variant has been reported in three individuals affected with lung cancer (PMID: 27242894), in a family with suspected Li-Fraumeni syndrome (PMID: 21348412), in individuals affected with uveal melanoma (PMID: 29769598), and in two individuals undergoing genetic testing unselected for cancer history (PMID: 28861920). ClinVar contains an entry for this variant (Variation ID: 406605). This variant has been reported not to substantially affect TP53 protein function (PMID: 12826609, 30224644, 29979965). This variant disrupts the p.Ile254 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29070607). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Oct 25, 2021

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