NM_000546.6(TP53):c.869G>T (p.Arg290Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 14, 2021
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:: RCV001018200.4

Allele description [Variation Report for NM_000546.6(TP53):c.869G>T (p.Arg290Leu)]

NM_000546.6(TP53):c.869G>T (p.Arg290Leu)

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.869G>T (p.Arg290Leu)

HGVS:

NC_000017.11:g.7673751C>A
NG_017013.2:g.18800G>T
NM_000546.6:c.869G>TMANE SELECT
NM_001126112.3:c.869G>T
NM_001126113.3:c.869G>T
NM_001126114.3:c.869G>T
NM_001126115.2:c.473G>T
NM_001126116.2:c.473G>T
NM_001126117.2:c.473G>T
NM_001126118.2:c.752G>T
NM_001276695.3:c.752G>T
NM_001276696.3:c.752G>T
NM_001276697.3:c.392G>T
NM_001276698.3:c.392G>T
NM_001276699.3:c.392G>T
NM_001276760.3:c.752G>T
NM_001276761.3:c.752G>T
NP_000537.3:p.Arg290Leu
NP_000537.3:p.Arg290Leu
NP_001119584.1:p.Arg290Leu
NP_001119585.1:p.Arg290Leu
NP_001119586.1:p.Arg290Leu
NP_001119587.1:p.Arg158Leu
NP_001119588.1:p.Arg158Leu
NP_001119589.1:p.Arg158Leu
NP_001119590.1:p.Arg251Leu
NP_001263624.1:p.Arg251Leu
NP_001263625.1:p.Arg251Leu
NP_001263626.1:p.Arg131Leu
NP_001263627.1:p.Arg131Leu
NP_001263628.1:p.Arg131Leu
NP_001263689.1:p.Arg251Leu
NP_001263690.1:p.Arg251Leu
LRG_321t1:c.869G>T
LRG_321:g.18800G>T
LRG_321p1:p.Arg290Leu
NC_000017.10:g.7577069C>A
NM_000546.4:c.869G>T
NM_000546.5:c.869G>T

Protein change:

R131L

Links:

dbSNP: rs55819519

NCBI 1000 Genomes Browser:

rs55819519

Molecular consequence:

NM_000546.6:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.473G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.473G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.473G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.752G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.752G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.752G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.392G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.392G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.392G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.752G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.752G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001179400	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 14, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12826609, 16437140, 29979965, 30224644 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001179400

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 14, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]

PMID:: 12826609
PMCID:: PMC166245

Acute myelogenous leukemia in a patient with Li-Fraumeni syndrome treated with valproic acid, theophyllamine and all-trans retinoic acid: a case report.

Anensen N, Skavland J, Stapnes C, Ryningen A, Børresen-Dale AL, Gjertsen BT, Bruserud Ø.

Leukemia. 2006 Apr;20(4):734-6. No abstract available.

PubMed [citation]

PMID:: 16437140

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001179400.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.R290L variant (also known as c.869G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 869. The arginine at codon 290 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in a 51-year-old female with a personal history of breast cancer, three soft tissue sarcomas and anal carcinoma, the first sarcoma being diagnosed at the age of 28. This alteration was also reported in the woman's son, who had a rhabdomyosarcoma and died from acute leukemia at age 12 (Anensen N et al. Leukemia, 2006 Apr;20:734-6). This variant is in the DNA binding domain of the TP53 protein and is reported to have functional transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (Kotler E et al. Mol.Cell, 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.

#	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: Oct 26, 2024

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