U.S. flag

An official website of the United States government

NM_000546.6(TP53):c.772G>A (p.Glu258Lys) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 30, 2021
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:
RCV000161071.9

Allele description [Variation Report for NM_000546.6(TP53):c.772G>A (p.Glu258Lys)]

NM_000546.6(TP53):c.772G>A (p.Glu258Lys)

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.772G>A (p.Glu258Lys)
Other names:
p.E258K:GAA>AAA
HGVS:
  • NC_000017.11:g.7674191C>T
  • NG_017013.2:g.18360G>A
  • NM_000546.6:c.772G>AMANE SELECT
  • NM_001126112.3:c.772G>A
  • NM_001126113.3:c.772G>A
  • NM_001126114.3:c.772G>A
  • NM_001126115.2:c.376G>A
  • NM_001126116.2:c.376G>A
  • NM_001126117.2:c.376G>A
  • NM_001126118.2:c.655G>A
  • NM_001276695.3:c.655G>A
  • NM_001276696.3:c.655G>A
  • NM_001276697.3:c.295G>A
  • NM_001276698.3:c.295G>A
  • NM_001276699.3:c.295G>A
  • NM_001276760.3:c.655G>A
  • NM_001276761.3:c.655G>A
  • NP_000537.3:p.Glu258Lys
  • NP_000537.3:p.Glu258Lys
  • NP_001119584.1:p.Glu258Lys
  • NP_001119585.1:p.Glu258Lys
  • NP_001119586.1:p.Glu258Lys
  • NP_001119587.1:p.Glu126Lys
  • NP_001119588.1:p.Glu126Lys
  • NP_001119589.1:p.Glu126Lys
  • NP_001119590.1:p.Glu219Lys
  • NP_001263624.1:p.Glu219Lys
  • NP_001263625.1:p.Glu219Lys
  • NP_001263626.1:p.Glu99Lys
  • NP_001263627.1:p.Glu99Lys
  • NP_001263628.1:p.Glu99Lys
  • NP_001263689.1:p.Glu219Lys
  • NP_001263690.1:p.Glu219Lys
  • LRG_321t1:c.772G>A
  • LRG_321:g.18360G>A
  • LRG_321p1:p.Glu258Lys
  • NC_000017.10:g.7577509C>T
  • NM_000546.4:c.772G>A
  • NM_000546.5:c.772G>A
  • P04637:p.Glu258Lys
Protein change:
E126K; GLU258LYS
Links:
UniProtKB: P04637#VAR_005991; OMIM: 191170.0002; dbSNP: rs121912652
NCBI 1000 Genomes Browser:
rs121912652
Molecular consequence:
  • NM_000546.6:c.772G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.772G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.772G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.772G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000211805GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Pathogenic
(Nov 30, 2021) 		germlineclinical testing

Citation Link,

SCV000602278Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)		Pathogenic
(Oct 6, 2021) 		unknownclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, et al.

Science. 1990 Nov 30;250(4985):1233-8. Erratum in: Science. 1993 Feb 12;259(5097):878..

PubMed [citation]
PMID:
1978757

Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation.

Malcikova J, Tichy B, Damborsky J, Kabathova J, Trbusek M, Mayer J, Pospisilova S.

Biol Chem. 2010 Feb-Mar;391(2-3):197-205. doi: 10.1515/bc.2010.027.

PubMed [citation]
PMID:
20128691
See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV000211805.12

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

Description

Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Frebourg 1992, Flaman 1998, Waddell 2001, Kato 2003, Malcikova 2010, Monti 2011, Kotler 2018); Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15722483, 11593407, 30720243, 21343334, 17606709, 9364015, 7829527, 1458490, 10719737, 21121188, 7732013, 8252037, 10753186, 11429705, 16492679, 9546439, 9635858, 1631137, 21232794, 8570655, 14559903, 12909720, 8313374, 29625052, 29979965, 21552135, 30840781, 30577483, 33309985, 15510160, 1978757, 20128691)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000602278.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in affected individuals with Li-Fraumeni Syndrome, glioblastoma, gastric, brain, and colon cancers (PMIDs: 29625052 (2018), 26425688 (2015), 21552135 (2011), 17606709 (2007), and 1978757 (1990)). Functional studies showed severe deficiencies in DNA binding and transactivation of transcriptional targets (PMIDs: 21343334 (2011) and 20128691 (2010)). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Feb 25, 2025