NM_000546.6(TP53):c.74T>G (p.Leu25Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 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:: RCV002391618.2

Allele description [Variation Report for NM_000546.6(TP53):c.74T>G (p.Leu25Arg)]

NM_000546.6(TP53):c.74T>G (p.Leu25Arg)

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.74T>G (p.Leu25Arg)

HGVS:

NC_000017.11:g.7676521A>C
NG_017013.2:g.16030T>G
NM_000546.6:c.74T>GMANE SELECT
NM_001126112.3:c.74T>G
NM_001126113.3:c.74T>G
NM_001126114.3:c.74T>G
NM_001126118.2:c.-161T>G
NM_001276695.3:c.-44T>G
NM_001276696.3:c.-44T>G
NM_001276760.3:c.-44T>G
NM_001276761.3:c.-44T>G
NM_001407262.1:c.74T>G
NM_001407263.1:c.-44T>G
NM_001407264.1:c.74T>G
NM_001407265.1:c.-44T>G
NM_001407266.1:c.74T>G
NM_001407267.1:c.-44T>G
NM_001407268.1:c.74T>G
NM_001407269.1:c.-44T>G
NM_001407270.1:c.74T>G
NM_001407271.1:c.-44T>G
NP_000537.3:p.Leu25Arg
NP_000537.3:p.Leu25Arg
NP_001119584.1:p.Leu25Arg
NP_001119584.1:p.Leu25Arg
NP_001119585.1:p.Leu25Arg
NP_001119585.1:p.Leu25Arg
NP_001119586.1:p.Leu25Arg
NP_001119586.1:p.Leu25Arg
NP_001394191.1:p.Leu25Arg
NP_001394193.1:p.Leu25Arg
NP_001394195.1:p.Leu25Arg
NP_001394197.1:p.Leu25Arg
NP_001394199.1:p.Leu25Arg
LRG_321t1:c.74T>G
LRG_321t2:c.74T>G
LRG_321t3:c.74T>G
LRG_321t4:c.74T>G
LRG_321t8:c.-161T>G
LRG_321:g.16030T>G
LRG_321:p.Leu25Arg
LRG_321p1:p.Leu25Arg
LRG_321p3:p.Leu25Arg
LRG_321p4:p.Leu25Arg
NC_000017.10:g.7579839A>C
NM_000546.4:c.74T>G
NM_000546.5:c.74T>G
NM_001126112.2:c.74T>G
NM_001126113.2:c.74T>G
NM_001126114.2:c.74T>G
NM_001126118.1:c.-161T>G
NR_176326.1:n.216T>G

Protein change:

L25R

Molecular consequence:

NM_001126118.2:c.-161T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-44T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-44T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-44T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-44T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.74T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.74T>G - 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
SCV002675063	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 13, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12826609, 30224644 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002675063

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 13, 2021)

germline

clinical testing

PubMed (2)
[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

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]

PMID:: 30224644
PMCID:: PMC6168352

Details of each submission

From Ambry Genetics, SCV002675063.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.74T>G variant (also known as p.L25R), located in coding exon 1 of the TP53 gene, results from a T to G substitution at nucleotide position 74. The amino acid change results in leucine to arginine at codon 25, an amino acid with dissimilar properties. This variant is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited 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: May 1, 2024

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