NM_000546.6(TP53):c.581T>G (p.Leu194Arg) AND Li-Fraumeni syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 15, 2024
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:: RCV004022229.1

Allele description [Variation Report for NM_000546.6(TP53):c.581T>G (p.Leu194Arg)]

NM_000546.6(TP53):c.581T>G (p.Leu194Arg)

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.581T>G (p.Leu194Arg)

HGVS:

NC_000017.11:g.7674950A>C
NG_017013.2:g.17601T>G
NM_000546.6:c.581T>GMANE SELECT
NM_001126112.3:c.581T>G
NM_001126113.3:c.581T>G
NM_001126114.3:c.581T>G
NM_001126115.2:c.185T>G
NM_001126116.2:c.185T>G
NM_001126117.2:c.185T>G
NM_001126118.2:c.464T>G
NM_001276695.3:c.464T>G
NM_001276696.3:c.464T>G
NM_001276697.3:c.104T>G
NM_001276698.3:c.104T>G
NM_001276699.3:c.104T>G
NM_001276760.3:c.464T>G
NM_001276761.3:c.464T>G
NP_000537.3:p.Leu194Arg
NP_000537.3:p.Leu194Arg
NP_001119584.1:p.Leu194Arg
NP_001119585.1:p.Leu194Arg
NP_001119586.1:p.Leu194Arg
NP_001119587.1:p.Leu62Arg
NP_001119588.1:p.Leu62Arg
NP_001119589.1:p.Leu62Arg
NP_001119590.1:p.Leu155Arg
NP_001263624.1:p.Leu155Arg
NP_001263625.1:p.Leu155Arg
NP_001263626.1:p.Leu35Arg
NP_001263627.1:p.Leu35Arg
NP_001263628.1:p.Leu35Arg
NP_001263689.1:p.Leu155Arg
NP_001263690.1:p.Leu155Arg
LRG_321t1:c.581T>G
LRG_321:g.17601T>G
LRG_321p1:p.Leu194Arg
NC_000017.10:g.7578268A>C
NM_000546.4:c.581T>G
NM_000546.5:c.581T>G

Protein change:

L155R

Links:

dbSNP: rs1057519998

NCBI 1000 Genomes Browser:

rs1057519998

Molecular consequence:

NM_000546.6:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004932075	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 15, 2024)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12509279, 15077194 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004932075

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Feb 15, 2024)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel p53 mutant retained functional activity in lung carcinomas.

Ko JL, Chiao MC, Chang SL, Lin P, Lin JC, Sheu GT, Lee H.

DNA Repair (Amst). 2002 Sep 4;1(9):755-62.

PubMed [citation]

PMID:: 12509279

Tumor-derived p53 mutants induce oncogenesis by transactivating growth-promoting genes.

Scian MJ, Stagliano KE, Deb D, Ellis MA, Carchman EH, Das A, Valerie K, Deb SP, Deb S.

Oncogene. 2004 May 27;23(25):4430-43.

PubMed [citation]

PMID:: 15077194

Details of each submission

From Myriad Genetics, Inc., SCV004932075.1

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

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 12509279, 15077194]. This variant is expected to disrupt protein structure [Myriad internal data].

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

Last Updated: May 16, 2025

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