NM_000546.6(TP53):c.839G>A (p.Arg280Lys) AND Li-Fraumeni syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 2023
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:: RCV000633356.8

Allele description

NM_000546.6(TP53):c.839G>A (p.Arg280Lys)

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.839G>A (p.Arg280Lys)

HGVS:

NC_000017.11:g.7673781C>T
NG_017013.2:g.18770G>A
NM_000546.6:c.839G>AMANE SELECT
NM_001126112.3:c.839G>A
NM_001126113.3:c.839G>A
NM_001126114.3:c.839G>A
NM_001126115.2:c.443G>A
NM_001126116.2:c.443G>A
NM_001126117.2:c.443G>A
NM_001126118.2:c.722G>A
NM_001276695.3:c.722G>A
NM_001276696.3:c.722G>A
NM_001276697.3:c.362G>A
NM_001276698.3:c.362G>A
NM_001276699.3:c.362G>A
NM_001276760.3:c.722G>A
NM_001276761.3:c.722G>A
NP_000537.3:p.Arg280Lys
NP_000537.3:p.Arg280Lys
NP_001119584.1:p.Arg280Lys
NP_001119585.1:p.Arg280Lys
NP_001119586.1:p.Arg280Lys
NP_001119587.1:p.Arg148Lys
NP_001119588.1:p.Arg148Lys
NP_001119589.1:p.Arg148Lys
NP_001119590.1:p.Arg241Lys
NP_001263624.1:p.Arg241Lys
NP_001263625.1:p.Arg241Lys
NP_001263626.1:p.Arg121Lys
NP_001263627.1:p.Arg121Lys
NP_001263628.1:p.Arg121Lys
NP_001263689.1:p.Arg241Lys
NP_001263690.1:p.Arg241Lys
LRG_321t1:c.839G>A
LRG_321:g.18770G>A
LRG_321p1:p.Arg280Lys
NC_000017.10:g.7577099C>T
NM_000546.4:c.839G>A
NM_000546.5:c.839G>A

Protein change:

R121K

Links:

dbSNP: rs121912660

NCBI 1000 Genomes Browser:

rs121912660

Molecular consequence:

NM_000546.6:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000754578	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 19, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10589545, 23334668, 29979965, 30224644, 12826609, 20128691, 21343334, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754578

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 19, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Germline mutations of p53 but not p16/CDKN2 or PTEN/MMAC1 tumor suppressor genes predispose to gliomas. The ANOCEF Group. Association des NeuroOncologues d'Expression Française.

Zhou XP, Sanson M, Hoang-Xuan K, Robin E, Taillandier L, He J, Mokhtari K, Cornu P, Delattre JY, Thomas G, Hamelin R.

Ann Neurol. 1999 Dec;46(6):913-6.

PubMed [citation]

PMID:: 10589545

The genomic landscape of hypodiploid acute lymphoblastic leukemia.

Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, et al.

Nat Genet. 2013 Mar;45(3):242-52. doi: 10.1038/ng.2532. Epub 2013 Jan 20.

PubMed [citation]

PMID:: 23334668
PMCID:: PMC3919793

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000754578.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 280 of the TP53 protein (p.Arg280Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with acute lymphoblastic leukemia, breast cancer, and/or glioblastoma (PMID: 10589545, 23334668; Invitae). ClinVar contains an entry for this variant (Variation ID: 376657). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 20128691, 21343334). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 16, 2024

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