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NM_000546.6(TP53):c.353C>T (p.Thr118Ile) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 8, 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:
RCV000526166.10

Allele description [Variation Report for NM_000546.6(TP53):c.353C>T (p.Thr118Ile)]

NM_000546.6(TP53):c.353C>T (p.Thr118Ile)

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.353C>T (p.Thr118Ile)
Other names:
NM_000546.5(TP53):c.353C>T; p.Thr118Ile
HGVS:
  • NC_000017.11:g.7676016G>A
  • NG_017013.2:g.16535C>T
  • NM_000546.6:c.353C>TMANE SELECT
  • NM_001126112.3:c.353C>T
  • NM_001126113.3:c.353C>T
  • NM_001126114.3:c.353C>T
  • NM_001126118.2:c.236C>T
  • NM_001276695.3:c.236C>T
  • NM_001276696.3:c.236C>T
  • NM_001276760.3:c.236C>T
  • NM_001276761.3:c.236C>T
  • NP_000537.3:p.Thr118Ile
  • NP_000537.3:p.Thr118Ile
  • NP_001119584.1:p.Thr118Ile
  • NP_001119585.1:p.Thr118Ile
  • NP_001119586.1:p.Thr118Ile
  • NP_001119590.1:p.Thr79Ile
  • NP_001263624.1:p.Thr79Ile
  • NP_001263625.1:p.Thr79Ile
  • NP_001263689.1:p.Thr79Ile
  • NP_001263690.1:p.Thr79Ile
  • LRG_321t1:c.353C>T
  • LRG_321:g.16535C>T
  • LRG_321p1:p.Thr118Ile
  • NC_000017.10:g.7579334G>A
  • NM_000546.4:c.353C>T
  • NM_000546.5:c.353C>T
Protein change:
T118I
Links:
dbSNP: rs1064794141
NCBI 1000 Genomes Browser:
rs1064794141
Molecular consequence:
  • NM_000546.6:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.236C>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
SCV000629806Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 8, 2023) 		germlineclinical testing

PubMed (4)
[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

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]
PMID:
29979965

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]
PMID:
30224644
PMCID:
PMC6168352
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000629806.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 118 of the TP53 protein (p.Thr118Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 419837). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). 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: Nov 10, 2024