NM_000546.6(TP53):c.880G>T (p.Glu294Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 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:: RCV002374641.2

Allele description [Variation Report for NM_000546.6(TP53):c.880G>T (p.Glu294Ter)]

NM_000546.6(TP53):c.880G>T (p.Glu294Ter)

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.880G>T (p.Glu294Ter)

HGVS:

NC_000017.11:g.7673740C>A
NG_017013.2:g.18811G>T
NM_000546.6:c.880G>TMANE SELECT
NM_001126112.3:c.880G>T
NM_001126113.3:c.880G>T
NM_001126114.3:c.880G>T
NM_001126115.2:c.484G>T
NM_001126116.2:c.484G>T
NM_001126117.2:c.484G>T
NM_001126118.2:c.763G>T
NM_001276695.3:c.763G>T
NM_001276696.3:c.763G>T
NM_001276697.3:c.403G>T
NM_001276698.3:c.403G>T
NM_001276699.3:c.403G>T
NM_001276760.3:c.763G>T
NM_001276761.3:c.763G>T
NP_000537.3:p.Glu294Ter
NP_001119584.1:p.Glu294Ter
NP_001119585.1:p.Glu294Ter
NP_001119586.1:p.Glu294Ter
NP_001119587.1:p.Glu162Ter
NP_001119588.1:p.Glu162Ter
NP_001119589.1:p.Glu162Ter
NP_001119590.1:p.Glu255Ter
NP_001263624.1:p.Glu255Ter
NP_001263625.1:p.Glu255Ter
NP_001263626.1:p.Glu135Ter
NP_001263627.1:p.Glu135Ter
NP_001263628.1:p.Glu135Ter
NP_001263689.1:p.Glu255Ter
NP_001263690.1:p.Glu255Ter
LRG_321:g.18811G>T
NC_000017.10:g.7577058C>A
NM_000546.4:c.880G>T

Protein change:

E135*

Links:

dbSNP: rs1057520607

NCBI 1000 Genomes Browser:

rs1057520607

Molecular consequence:

NM_000546.6:c.880G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.880G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.880G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.880G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.484G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126116.2:c.484G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126117.2:c.484G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.763G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.763G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.763G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.403G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276698.3:c.403G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276699.3:c.403G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.763G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.763G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002687971	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17591842, 24251760 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002687971

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 31, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability.

Veschi S, Aceto G, Scioletti AP, Gatta V, Palka G, Cama A, Mariani-Costantini R, Battista P, Calò V, Barbera F, Bazan V, Russo A, Stuppia L.

Ann Oncol. 2007 Jun;18 Suppl 6:vi86-92.

PubMed [citation]

PMID:: 17591842

Spitzoid melanoma in a child with Li-Fraumeni syndrome.

Kollipara R, Cooley LD, Horii KA, Hetherington ML, Leboit PE, Singh V, Zwick DL.

Pediatr Dev Pathol. 2014 Jan-Feb;17(1):64-9. doi: 10.2350/13-09-1380-CR.1. Epub 2013 Nov 19.

PubMed [citation]

PMID:: 24251760

Details of each submission

From Ambry Genetics, SCV002687971.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.E294* pathogenic mutation (also known as c.880G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 880. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This pathogenic mutation has been reported in a patient with bilateral breast cancers diagnosed at age 33 and 41 whose son was reported to have an osteosarcoma diagnosed at age 15 (Veschi S et al. Ann Oncol, 2007 Jun;18 Suppl 6:vi86-92). This mutation was also reported in a pediatric patient with a personal history of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia (Kollipara R et al. Pediatr Dev Pathol Nov;17:64-9). This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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: Jul 15, 2024

ClinVar

Relating variation to medicine