NM_000546.6(TP53):c.452C>G (p.Pro151Arg) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 3, 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:: RCV000633382.9

Allele description [Variation Report for NM_000546.6(TP53):c.452C>G (p.Pro151Arg)]

NM_000546.6(TP53):c.452C>G (p.Pro151Arg)

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.452C>G (p.Pro151Arg)

HGVS:

NC_000017.11:g.7675160G>C
NG_017013.2:g.17391C>G
NM_000546.4:c.452C>G
NM_000546.6:c.452C>GMANE SELECT
NM_001126112.3:c.452C>G
NM_001126113.3:c.452C>G
NM_001126114.3:c.452C>G
NM_001126115.2:c.56C>G
NM_001126116.2:c.56C>G
NM_001126117.2:c.56C>G
NM_001126118.2:c.335C>G
NM_001276695.3:c.335C>G
NM_001276696.3:c.335C>G
NM_001276697.3:c.-26C>G
NM_001276698.3:c.-26C>G
NM_001276699.3:c.-26C>G
NM_001276760.3:c.335C>G
NM_001276761.3:c.335C>G
NP_000537.3:p.Pro151Arg
NP_000537.3:p.Pro151Arg
NP_001119584.1:p.Pro151Arg
NP_001119585.1:p.Pro151Arg
NP_001119586.1:p.Pro151Arg
NP_001119587.1:p.Pro19Arg
NP_001119588.1:p.Pro19Arg
NP_001119589.1:p.Pro19Arg
NP_001119590.1:p.Pro112Arg
NP_001263624.1:p.Pro112Arg
NP_001263625.1:p.Pro112Arg
NP_001263689.1:p.Pro112Arg
NP_001263690.1:p.Pro112Arg
LRG_321t1:c.452C>G
LRG_321:g.17391C>G
LRG_321p1:p.Pro151Arg
NC_000017.10:g.7578478G>C
NM_000546.5:c.452C>G

Protein change:

P112R

Links:

dbSNP: rs1057520000

NCBI 1000 Genomes Browser:

rs1057520000

Molecular consequence:

NM_001276697.3:c.-26C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-26C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-26C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.452C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.452C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.452C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.452C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.56C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.56C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.56C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.335C>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
SCV000754604	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 3, 2024)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 27489289, 29979965, 30224644, 7881428, 12826609, 17606709, 20522432, 25584008, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754604

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 3, 2024)

germline

clinical testing

PubMed (9)
[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

Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer.

Parsons HA, Beaver JA, Cimino-Mathews A, Ali SM, Axilbund J, Chu D, Connolly RM, Cochran RL, Croessmann S, Clark TA, Gocke CD, Jeter SC, Kennedy MR, Lauring J, Lee J, Lipson D, Miller VA, Otto GA, Rosner GL, Ross JS, Slater S, Stephens PJ, et al.

Clin Cancer Res. 2017 Jan 15;23(2):379-386. doi: 10.1158/1078-0432.CCR-16-1543. Epub 2016 Aug 3.

PubMed [citation]

PMID:: 27489289
PMCID:: PMC5241251

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

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754604.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 151 of the TP53 protein (p.Pro151Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Li-Fraumeni syndrome (PMID: 27489289; Invitae). ClinVar contains an entry for this variant (Variation ID: 376640). 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 with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). This variant disrupts the p.Pro151 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7881428, 12826609, 17606709, 20522432, 25584008). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024

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