NM_000546.6(TP53):c.861G>C (p.Glu287Asp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 2016
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:: RCV000481706.2

Allele description [Variation Report for NM_000546.6(TP53):c.861G>C (p.Glu287Asp)]

NM_000546.6(TP53):c.861G>C (p.Glu287Asp)

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.861G>C (p.Glu287Asp)

HGVS:

NC_000017.11:g.7673759C>G
NG_017013.2:g.18792G>C
NM_000546.6:c.861G>CMANE SELECT
NM_001126112.3:c.861G>C
NM_001126113.3:c.861G>C
NM_001126114.3:c.861G>C
NM_001126115.2:c.465G>C
NM_001126116.2:c.465G>C
NM_001126117.2:c.465G>C
NM_001126118.2:c.744G>C
NM_001276695.3:c.744G>C
NM_001276696.3:c.744G>C
NM_001276697.3:c.384G>C
NM_001276698.3:c.384G>C
NM_001276699.3:c.384G>C
NM_001276760.3:c.744G>C
NM_001276761.3:c.744G>C
NP_000537.3:p.Glu287Asp
NP_000537.3:p.Glu287Asp
NP_001119584.1:p.Glu287Asp
NP_001119585.1:p.Glu287Asp
NP_001119586.1:p.Glu287Asp
NP_001119587.1:p.Glu155Asp
NP_001119588.1:p.Glu155Asp
NP_001119589.1:p.Glu155Asp
NP_001119590.1:p.Glu248Asp
NP_001263624.1:p.Glu248Asp
NP_001263625.1:p.Glu248Asp
NP_001263626.1:p.Glu128Asp
NP_001263627.1:p.Glu128Asp
NP_001263628.1:p.Glu128Asp
NP_001263689.1:p.Glu248Asp
NP_001263690.1:p.Glu248Asp
LRG_321t1:c.861G>C
LRG_321:g.18792G>C
LRG_321p1:p.Glu287Asp
NC_000017.10:g.7577077C>G
NM_000546.4:c.861G>C
NM_000546.5:c.861G>C

Protein change:

E128D

Links:

dbSNP: rs748891343

NCBI 1000 Genomes Browser:

rs748891343

Molecular consequence:

NM_000546.6:c.861G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.861G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.861G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.861G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.465G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.465G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.465G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.744G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.744G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.744G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.384G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.384G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.384G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.744G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.744G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000571522	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Aug 29, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000571522

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Aug 29, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000571522.3

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

Description

This variant is denoted TP53 c.861G>C at the cDNA level, p.Glu287Asp (E287D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAG>GAC). This variant has been observed as being apparently somatically acquired in tumor specimens (Bartkova 2012, Gatalica 2014) and is reported as having functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Glu287Asp was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. TP53 Glu287Asp occurs at a position where amino acids with properties similar to Glutamic Acid are tolerated across species and is located in the DNA binding domain (Bode 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether TP53 Glu287Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

#	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

Last Updated: Oct 20, 2024

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