NM_000546.6(TP53):c.202G>T (p.Glu68Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 5, 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:: RCV000210192.6

Allele description [Variation Report for NM_000546.6(TP53):c.202G>T (p.Glu68Ter)]

NM_000546.6(TP53):c.202G>T (p.Glu68Ter)

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.202G>T (p.Glu68Ter)

HGVS:

NC_000017.11:g.7676167C>A
NG_017013.2:g.16384G>T
NM_000546.6:c.202G>TMANE SELECT
NM_001126112.3:c.202G>T
NM_001126113.3:c.202G>T
NM_001126114.3:c.202G>T
NM_001126118.2:c.85G>T
NM_001276695.3:c.85G>T
NM_001276696.3:c.85G>T
NM_001276760.3:c.85G>T
NM_001276761.3:c.85G>T
NP_000537.3:p.Glu68Ter
NP_000537.3:p.Glu68Ter
NP_001119584.1:p.Glu68Ter
NP_001119585.1:p.Glu68Ter
NP_001119586.1:p.Glu68Ter
NP_001119590.1:p.Glu29Ter
NP_001263624.1:p.Glu29Ter
NP_001263625.1:p.Glu29Ter
NP_001263689.1:p.Glu29Ter
NP_001263690.1:p.Glu29Ter
LRG_321t1:c.202G>T
LRG_321:g.16384G>T
LRG_321p1:p.Glu68Ter
NC_000017.10:g.7579485C>A
NM_000546.4:c.202G>T
NM_000546.5:c.202G>T

Protein change:

E29*

Links:

dbSNP: rs869312782

NCBI 1000 Genomes Browser:

rs869312782

Molecular consequence:

NM_000546.6:c.202G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.202G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.202G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.202G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.85G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.85G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.85G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.85G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.85G>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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
SCV000266134	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Shirts et al. (Genet Med 2016))	Pathogenic (Nov 20, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002582625	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]
SCV005177936	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 5, 2024)	germline	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

SCV000266134

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Shirts et al. (Genet Med 2016))

Pathogenic
(Nov 20, 2015)

germline

clinical testing

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

SCV002582625

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]

SCV005177936

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 5, 2024)

germline

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	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	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

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]

PMID:: 26845104

Details of each submission

From University of Washington Department of Laboratory Medicine, University of Washington, SCV000266134.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002582625.1

#	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 Ambry Genetics, SCV005177936.1

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

Description

The p.E68* pathogenic mutation (also known as c.202G>T), located in coding exon 3 of the TP53 gene, results from a G to T substitution at nucleotide position 202. This changes the amino acid from a glutamic acid to a stop codon within coding exon 3. This variant was detected in a proband meeting revised Chompret 2015 criteria (Ambry internal data). This variant was also detected in a patient with bilateral breast cancer at age 40 (Shirts BH et al. Genet Med, 2016 Oct;18:974-81). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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