NM_000546.6(TP53):c.726C>G (p.Cys242Trp) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV003621530.2

Allele description [Variation Report for NM_000546.6(TP53):c.726C>G (p.Cys242Trp)]

NM_000546.6(TP53):c.726C>G (p.Cys242Trp)

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.726C>G (p.Cys242Trp)

HGVS:

NC_000017.11:g.7674237G>C
NG_017013.2:g.18314C>G
NM_000546.6:c.726C>GMANE SELECT
NM_001126112.3:c.726C>G
NM_001126113.3:c.726C>G
NM_001126114.3:c.726C>G
NM_001126115.2:c.330C>G
NM_001126116.2:c.330C>G
NM_001126117.2:c.330C>G
NM_001126118.2:c.609C>G
NM_001276695.3:c.609C>G
NM_001276696.3:c.609C>G
NM_001276697.3:c.249C>G
NM_001276698.3:c.249C>G
NM_001276699.3:c.249C>G
NM_001276760.3:c.609C>G
NM_001276761.3:c.609C>G
NP_000537.3:p.Cys242Trp
NP_001119584.1:p.Cys242Trp
NP_001119585.1:p.Cys242Trp
NP_001119586.1:p.Cys242Trp
NP_001119587.1:p.Cys110Trp
NP_001119588.1:p.Cys110Trp
NP_001119589.1:p.Cys110Trp
NP_001119590.1:p.Cys203Trp
NP_001263624.1:p.Cys203Trp
NP_001263625.1:p.Cys203Trp
NP_001263626.1:p.Cys83Trp
NP_001263627.1:p.Cys83Trp
NP_001263628.1:p.Cys83Trp
NP_001263689.1:p.Cys203Trp
NP_001263690.1:p.Cys203Trp
LRG_321:g.18314C>G
NC_000017.10:g.7577555G>C

Protein change:

C110W

Links:

dbSNP: rs375874539

NCBI 1000 Genomes Browser:

rs375874539

Molecular consequence:

NM_000546.6:c.726C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.726C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.726C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.726C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.330C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.330C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.330C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.609C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.609C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.609C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.249C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.249C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.249C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.609C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.609C>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004375788	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 9, 2023)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 8164043, 9364015, 19930417, 20407015, 21343334, 25896519, 27276934, 12826609, 29979965, 30224644, 32959997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004375788

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 9, 2023)

germline

clinical testing

PubMed (12)
[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

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

McIntyre JF, Smith-Sorensen B, Friend SH, Kassell J, Borresen AL, Yan YX, Russo C, Sato J, Barbier N, Miser J, et al.

J Clin Oncol. 1994 May;12(5):925-30.

PubMed [citation]

PMID:: 8164043

Simple identification of dominant p53 mutants by a yeast functional assay.

Inga A, Cresta S, Monti P, Aprile A, Scott G, Abbondandolo A, Iggo R, Fronza G.

Carcinogenesis. 1997 Oct;18(10):2019-21.

PubMed [citation]

PMID:: 9364015

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004375788.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys242 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8164043, 9364015, 19930417, 20407015, 21343334, 25896519, 27276934). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 376580). This missense change has been observed in individual(s) with early onset breast cancer (PMID: 32959997). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 242 of the TP53 protein (p.Cys242Trp).

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine