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NM_000546.6(TP53):c.797G>A (p.Gly266Glu) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 7, 2019
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:
RCV000255749.7

Allele description [Variation Report for NM_000546.6(TP53):c.797G>A (p.Gly266Glu)]

NM_000546.6(TP53):c.797G>A (p.Gly266Glu)

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.797G>A (p.Gly266Glu)
HGVS:
  • NC_000017.11:g.7673823C>T
  • NG_017013.2:g.18728G>A
  • NM_000546.6:c.797G>AMANE SELECT
  • NM_001126112.3:c.797G>A
  • NM_001126113.3:c.797G>A
  • NM_001126114.3:c.797G>A
  • NM_001126115.2:c.401G>A
  • NM_001126116.2:c.401G>A
  • NM_001126117.2:c.401G>A
  • NM_001126118.2:c.680G>A
  • NM_001276695.3:c.680G>A
  • NM_001276696.3:c.680G>A
  • NM_001276697.3:c.320G>A
  • NM_001276698.3:c.320G>A
  • NM_001276699.3:c.320G>A
  • NM_001276760.3:c.680G>A
  • NM_001276761.3:c.680G>A
  • NP_000537.3:p.Gly266Glu
  • NP_000537.3:p.Gly266Glu
  • NP_001119584.1:p.Gly266Glu
  • NP_001119585.1:p.Gly266Glu
  • NP_001119586.1:p.Gly266Glu
  • NP_001119587.1:p.Gly134Glu
  • NP_001119587.1:p.Gly134Glu
  • NP_001119588.1:p.Gly134Glu
  • NP_001119589.1:p.Gly134Glu
  • NP_001119590.1:p.Gly227Glu
  • NP_001263624.1:p.Gly227Glu
  • NP_001263625.1:p.Gly227Glu
  • NP_001263626.1:p.Gly107Glu
  • NP_001263627.1:p.Gly107Glu
  • NP_001263628.1:p.Gly107Glu
  • NP_001263689.1:p.Gly227Glu
  • NP_001263690.1:p.Gly227Glu
  • LRG_321t1:c.797G>A
  • LRG_321t5:c.401G>A
  • LRG_321:g.18728G>A
  • LRG_321p1:p.Gly266Glu
  • LRG_321p5:p.Gly134Glu
  • NC_000017.10:g.7577141C>T
  • NM_000546.4:c.797G>A
  • NM_000546.5:c.797G>A
  • NM_001126115.1:c.401G>A
Protein change:
G107E
Links:
dbSNP: rs193920774
NCBI 1000 Genomes Browser:
rs193920774
Molecular consequence:
  • NM_000546.6:c.797G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.797G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.797G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.797G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.680G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000322130GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Jan 7, 2019) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000322130.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted TP53 c.797G>A at the cDNA level, p.Gly266Glu (G266E) at the protein level, and results in the change of a Glycine to a Glutamic Acid (GGA>GAA). This variant has been observed in at least one individual with childhood-onset medulloblastoma and another with personal/family reportedly suggestive of Li-Fraumeni syndrome (Bougeard 2008, Rausch 2012). Functional studies have consistently found that TP53 Gly266Glu is not capable of transactivating typical p53 response elements, leads to a loss of growth suppression activity, and does not exhibit a dominant-negative effect (Campomenosi 2001, Monti 2002, Grochova 2008, Slovackova 2010, Kotler 2018). This variant is reported as having non-functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Gly266Glu was not observed in large population cohorts (Lek 2016). This variant is located in the DNA-binding domain (Bode 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on the currently available information, we consider TP53 Gly266Glu to be a likely pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 29, 2024