NM_000546.6(TP53):c.725G>A (p.Cys242Tyr) AND Li-Fraumeni syndrome 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Feb 16, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002288484.6

Allele description [Variation Report for NM_000546.6(TP53):c.725G>A (p.Cys242Tyr)]

NM_000546.6(TP53):c.725G>A (p.Cys242Tyr)

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.725G>A (p.Cys242Tyr)

HGVS:

NC_000017.11:g.7674238C>T
NG_017013.2:g.18313G>A
NM_000546.6:c.725G>AMANE SELECT
NM_001126112.3:c.725G>A
NM_001126113.3:c.725G>A
NM_001126114.3:c.725G>A
NM_001126115.2:c.329G>A
NM_001126116.2:c.329G>A
NM_001126117.2:c.329G>A
NM_001126118.2:c.608G>A
NM_001276695.3:c.608G>A
NM_001276696.3:c.608G>A
NM_001276697.3:c.248G>A
NM_001276698.3:c.248G>A
NM_001276699.3:c.248G>A
NM_001276760.3:c.608G>A
NM_001276761.3:c.608G>A
NP_000537.3:p.Cys242Tyr
NP_000537.3:p.Cys242Tyr
NP_001119584.1:p.Cys242Tyr
NP_001119585.1:p.Cys242Tyr
NP_001119586.1:p.Cys242Tyr
NP_001119587.1:p.Cys110Tyr
NP_001119588.1:p.Cys110Tyr
NP_001119589.1:p.Cys110Tyr
NP_001119590.1:p.Cys203Tyr
NP_001263624.1:p.Cys203Tyr
NP_001263625.1:p.Cys203Tyr
NP_001263626.1:p.Cys83Tyr
NP_001263627.1:p.Cys83Tyr
NP_001263628.1:p.Cys83Tyr
NP_001263689.1:p.Cys203Tyr
NP_001263690.1:p.Cys203Tyr
LRG_321t1:c.725G>A
LRG_321:g.18313G>A
LRG_321p1:p.Cys242Tyr
NC_000017.10:g.7577556C>T
NM_000546.4:c.725G>A
NM_000546.5:c.725G>A
P04637:p.Cys242Tyr
p.C242Y

Protein change:

C110Y; CYS242TYR

Links:

UniProtKB: P04637#VAR_045224; OMIM: 191170.0008; dbSNP: rs121912655

Molecular consequence:

NM_000546.6:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.329G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.329G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.329G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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
SCV002583130	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004048073	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004931268	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 16, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002583130

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004048073

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004931268

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Feb 16, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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

Details of each submission

From Genome-Nilou Lab, SCV002583130.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004048073.1

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

Description

The missense variant c.725G>A (p.Cys242Tyr) in TP53 gene has been reported in literature (Chang MT et.al.,2016). This pathogenic mutation is located in the functionally critical DNA binding domain, and it is one of four amino acid residues required for zinc binding and protein stabilization (Cho Y et al.). This variant has been reported to the ClinVar database as Pathogenic. The p.Cys242Tyr variant is reported with allele frequency of 0% in gnomAD exomes and novel in 1000 Genomes. The amino acid Cys at position 242 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Cys242Tyr in TP53 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004931268.1

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

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

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

Last Updated: Apr 12, 2026

ClinVar

Relating variation to medicine