NM_000546.6(TP53):c.772G>A (p.Glu258Lys) AND Li-Fraumeni syndrome 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 18, 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:: RCV000013141.28

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)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

Recent activity

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BREX-1 system phosphatase PglZ type A [Lactobacillus johnsonii]
BREX-1 system phosphatase PglZ type A [Lactobacillus johnsonii]
gi|502609142|ref|WP_012846183.1|

Protein
integrase [Pseudomonas sp. JY-Q]
integrase [Pseudomonas sp. JY-Q]
gi|1034244251|gnl|PRJNA283455|AA098 5|gb|ANI37287.1|

Protein
hypothetical protein AA098_27445 [Pseudomonas sp. JY-Q]
hypothetical protein AA098_27445 [Pseudomonas sp. JY-Q]
gi|1034244257|gnl|PRJNA283455|AA098 5|gb|ANI37293.1|

Protein
Invertebrate sample from Phymatotrichopsis omnivora
Invertebrate sample from Phymatotrichopsis omnivora

biosample
KAFR0H01370 [Kazachstania africana CBS 2517]
KAFR0H01370 [Kazachstania africana CBS 2517]
Gene ID:13887544

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033388	OMIM	no assertion criteria provided	Pathogenic (Aug 27, 2020)	germline	literature only	Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.,
SCV002583018	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033388

OMIM

no assertion criteria provided

Pathogenic
(Aug 27, 2020)

germline

literature only

Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.,

SCV002583018

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 18, 2022)

germline

clinical testing

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

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

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

Details of each submission

From OMIM, SCV000033388.2

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

Description

In a family with the Li-Fraumeni syndrome-1 (151623), Malkin et al. (1990) identified a G-to-A mutation at the first nucleotide of codon 258, resulting in substitution of lysine for glutamic acid (E258K).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002583018.1

#	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

Last Updated: Sep 29, 2024

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