NM_000546.6(TP53):c.794T>G (p.Leu265Arg) AND Li-Fraumeni syndrome

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 30, 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:: RCV003510234.1

Allele description

NM_000546.6(TP53):c.794T>G (p.Leu265Arg)

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.794T>G (p.Leu265Arg)

HGVS:

NC_000017.11:g.7673826A>C
NG_017013.2:g.18725T>G
NM_000546.6:c.794T>GMANE SELECT
NM_001126112.3:c.794T>G
NM_001126113.3:c.794T>G
NM_001126114.3:c.794T>G
NM_001126115.2:c.398T>G
NM_001126116.2:c.398T>G
NM_001126117.2:c.398T>G
NM_001126118.2:c.677T>G
NM_001276695.3:c.677T>G
NM_001276696.3:c.677T>G
NM_001276697.3:c.317T>G
NM_001276698.3:c.317T>G
NM_001276699.3:c.317T>G
NM_001276760.3:c.677T>G
NM_001276761.3:c.677T>G
NM_001407262.1:c.794T>G
NM_001407263.1:c.677T>G
NM_001407264.1:c.794T>G
NM_001407265.1:c.677T>G
NM_001407266.1:c.794T>G
NM_001407267.1:c.677T>G
NM_001407268.1:c.794T>G
NM_001407269.1:c.677T>G
NM_001407270.1:c.794T>G
NM_001407271.1:c.677T>G
NP_000537.3:p.Leu265Arg
NP_000537.3:p.Leu265Arg
NP_001119584.1:p.Leu265Arg
NP_001119584.1:p.Leu265Arg
NP_001119585.1:p.Leu265Arg
NP_001119585.1:p.Leu265Arg
NP_001119586.1:p.Leu265Arg
NP_001119586.1:p.Leu265Arg
NP_001119587.1:p.Leu133Arg
NP_001119587.1:p.Leu133Arg
NP_001119588.1:p.Leu133Arg
NP_001119588.1:p.Leu133Arg
NP_001119589.1:p.Leu133Arg
NP_001119589.1:p.Leu133Arg
NP_001119590.1:p.Leu226Arg
NP_001119590.1:p.Leu226Arg
NP_001263624.1:p.Leu226Arg
NP_001263625.1:p.Leu226Arg
NP_001263626.1:p.Leu106Arg
NP_001263627.1:p.Leu106Arg
NP_001263628.1:p.Leu106Arg
NP_001263689.1:p.Leu226Arg
NP_001263690.1:p.Leu226Arg
NP_001394191.1:p.Leu265Arg
NP_001394192.1:p.Leu226Arg
NP_001394193.1:p.Leu265Arg
NP_001394194.1:p.Leu226Arg
NP_001394195.1:p.Leu265Arg
NP_001394196.1:p.Leu226Arg
NP_001394197.1:p.Leu265Arg
NP_001394198.1:p.Leu226Arg
NP_001394199.1:p.Leu265Arg
NP_001394200.1:p.Leu226Arg
LRG_321t1:c.794T>G
LRG_321t2:c.794T>G
LRG_321t3:c.794T>G
LRG_321t4:c.794T>G
LRG_321t5:c.398T>G
LRG_321t6:c.398T>G
LRG_321t7:c.398T>G
LRG_321t8:c.677T>G
LRG_321:g.18725T>G
LRG_321:p.Leu265Arg
LRG_321p1:p.Leu265Arg
LRG_321p3:p.Leu265Arg
LRG_321p4:p.Leu265Arg
LRG_321p5:p.Leu133Arg
LRG_321p6:p.Leu133Arg
LRG_321p7:p.Leu133Arg
LRG_321p8:p.Leu226Arg
NC_000017.10:g.7577144A>C
NM_000546.5:c.794T>G
NM_001126112.2:c.794T>G
NM_001126113.2:c.794T>G
NM_001126114.2:c.794T>G
NM_001126115.1:c.398T>G
NM_001126116.1:c.398T>G
NM_001126117.1:c.398T>G
NM_001126118.1:c.677T>G
NR_176326.1:n.823T>G

Protein change:

L106R

Molecular consequence:

NM_000546.6:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.398T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.398T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.398T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.317T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.317T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.317T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.794T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176326.1:n.823T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Mus musculus MAP kinase kinase kinase 1 (Mekk1) mRNA, complete cds
Mus musculus MAP kinase kinase kinase 1 (Mekk1) mRNA, complete cds
gi|4583379|gb|AF117340.1|

Nucleotide
MULTISPECIES: 50S ribosomal protein L23 [Burkholderia]
MULTISPECIES: 50S ribosomal protein L23 [Burkholderia]
gi|490303958|ref|WP_004199275.1|

Protein
Mus musculus semaphorin cytoplasmic domain-associated protein 3B (Semcap3) mRNA,...
Mus musculus semaphorin cytoplasmic domain-associated protein 3B (Semcap3) mRNA, complete cds
gi|6651020|gb|AF127085.1|

Nucleotide
Salvelinus fontinalis voucher ROM:T01542-80198 small subunit ribosomal RNA gene,...
Salvelinus fontinalis voucher ROM:T01542-80198 small subunit ribosomal RNA gene, partial sequence
gi|2510895478|gb|OR052005.1|

Nucleotide
Francisella tularensis subsp. holarctica strain B.87 NODE_36_length_21163_cov_19...
Francisella tularensis subsp. holarctica strain B.87 NODE_36_length_21163_cov_1914.62_ID_6366, whole genome shotgun sequence
gi|1320543418|gb|PKBY01000036.1||gn :PKBY01|NODE_36_length_21163_cov_1914.62_ID_6366

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004328965	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 30, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004328965

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 30, 2023)

germline

clinical testing

PubMed (4)
[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

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

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004328965.1

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 265 of the TP53 protein (p.Leu265Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. 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. 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: Feb 20, 2024

ClinVar

Relating variation to medicine