NM_000546.6(TP53):c.337T>G (p.Phe113Val) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 5, 2024
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:: RCV000633376.13

Allele description [Variation Report for NM_000546.6(TP53):c.337T>G (p.Phe113Val)]

NM_000546.6(TP53):c.337T>G (p.Phe113Val)

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.337T>G (p.Phe113Val)

HGVS:

NC_000017.11:g.7676032A>C
NG_017013.2:g.16519T>G
NM_000546.6:c.337T>GMANE SELECT
NM_001126112.3:c.337T>G
NM_001126113.3:c.337T>G
NM_001126114.3:c.337T>G
NM_001126118.2:c.220T>G
NM_001276695.3:c.220T>G
NM_001276696.3:c.220T>G
NM_001276760.3:c.220T>G
NM_001276761.3:c.220T>G
NP_000537.3:p.Phe113Val
NP_000537.3:p.Phe113Val
NP_001119584.1:p.Phe113Val
NP_001119585.1:p.Phe113Val
NP_001119586.1:p.Phe113Val
NP_001119590.1:p.Phe74Val
NP_001263624.1:p.Phe74Val
NP_001263625.1:p.Phe74Val
NP_001263689.1:p.Phe74Val
NP_001263690.1:p.Phe74Val
LRG_321t1:c.337T>G
LRG_321:g.16519T>G
LRG_321p1:p.Phe113Val
NC_000017.10:g.7579350A>C
NM_000546.4:c.337T>G
NM_000546.5:c.337T>G
P04637:p.Phe113Val
p.F113V

Protein change:

F113V

Links:

UniProtKB: P04637#VAR_033033; dbSNP: rs587781642

Molecular consequence:

NM_000546.6:c.337T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.337T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.337T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.337T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.220T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.220T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.220T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.220T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.220T>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000754598	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 5, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12826609, 2826609, 29979965, 30224644, 17554785, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754598

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 5, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Severe, progressive herpetic whitlow caused by an acyclovir-resistant virus in a patient with AIDS.

Norris SA, Kessler HA, Fife KH.

J Infect Dis. 1988 Jan;157(1):209-10. No abstract available.

PubMed [citation]

PMID:: 2826609

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754598.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 113 of the TP53 protein (p.Phe113Val). 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: 141302). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 2826609, 29979965, 30224644). This variant disrupts the p.Phe113 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (PMID: 17554785; internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 14, 2026

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