NM_000546.6(TP53):c.853G>A (p.Glu285Lys) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 13, 2022
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:: RCV000633365.17

Allele description [Variation Report for NM_000546.6(TP53):c.853G>A (p.Glu285Lys)]

NM_000546.6(TP53):c.853G>A (p.Glu285Lys)

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.853G>A (p.Glu285Lys)

HGVS:

NC_000017.11:g.7673767C>T
NG_017013.2:g.18784G>A
NM_000546.6:c.853G>AMANE SELECT
NM_001126112.3:c.853G>A
NM_001126113.3:c.853G>A
NM_001126114.3:c.853G>A
NM_001126115.2:c.457G>A
NM_001126116.2:c.457G>A
NM_001126117.2:c.457G>A
NM_001126118.2:c.736G>A
NM_001276695.3:c.736G>A
NM_001276696.3:c.736G>A
NM_001276697.3:c.376G>A
NM_001276698.3:c.376G>A
NM_001276699.3:c.376G>A
NM_001276760.3:c.736G>A
NM_001276761.3:c.736G>A
NP_000537.3:p.Glu285Lys
NP_000537.3:p.Glu285Lys
NP_001119584.1:p.Glu285Lys
NP_001119585.1:p.Glu285Lys
NP_001119586.1:p.Glu285Lys
NP_001119587.1:p.Glu153Lys
NP_001119588.1:p.Glu153Lys
NP_001119589.1:p.Glu153Lys
NP_001119590.1:p.Glu246Lys
NP_001263624.1:p.Glu246Lys
NP_001263625.1:p.Glu246Lys
NP_001263626.1:p.Glu126Lys
NP_001263627.1:p.Glu126Lys
NP_001263628.1:p.Glu126Lys
NP_001263689.1:p.Glu246Lys
NP_001263690.1:p.Glu246Lys
LRG_321t1:c.853G>A
LRG_321:g.18784G>A
LRG_321p1:p.Glu285Lys
NC_000017.10:g.7577085C>T
NM_000546.4:c.853G>A
NM_000546.5:c.853G>A
NM_001126114.1:c.853G>A

Protein change:

E126K

Links:

dbSNP: rs112431538

NCBI 1000 Genomes Browser:

rs112431538

Molecular consequence:

NM_000546.6:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.736G>A - 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
SCV000754587	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 13, 2022)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 29979965, 30224644, 11051239, 22507745, 23894400, 9290701, 16861262, 17724467, 12826609, 18762572, 25584008, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754587

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 13, 2022)

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

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 (12)

Details of each submission

From Invitae, SCV000754587.7

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

Description

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: 420133). This missense change has been observed in individual(s) with breast cancer and sarcoma (PMID: 11051239, 22507745, 23894400). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 285 of the TP53 protein (p.Glu285Lys). Experimental studies have shown that this missense change affects TP53 function (PMID: 9290701, 12826609, 16861262, 17724467). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu285 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12826609, 18762572, 25584008). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

#	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: Jun 9, 2024

ClinVar

Relating variation to medicine