NM_000546.6(TP53):c.720T>G (p.Ser240Arg) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV000544531.7

Allele description [Variation Report for NM_000546.6(TP53):c.720T>G (p.Ser240Arg)]

NM_000546.6(TP53):c.720T>G (p.Ser240Arg)

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.720T>G (p.Ser240Arg)

HGVS:

NC_000017.11:g.7674243A>C
NG_017013.2:g.18308T>G
NM_000546.4:c.720T>G
NM_000546.6:c.720T>GMANE SELECT
NM_001126112.3:c.720T>G
NM_001126113.3:c.720T>G
NM_001126114.3:c.720T>G
NM_001126115.2:c.324T>G
NM_001126116.2:c.324T>G
NM_001126117.2:c.324T>G
NM_001126118.2:c.603T>G
NM_001276695.3:c.603T>G
NM_001276696.3:c.603T>G
NM_001276697.3:c.243T>G
NM_001276698.3:c.243T>G
NM_001276699.3:c.243T>G
NM_001276760.3:c.603T>G
NM_001276761.3:c.603T>G
NP_000537.3:p.Ser240Arg
NP_000537.3:p.Ser240Arg
NP_001119584.1:p.Ser240Arg
NP_001119585.1:p.Ser240Arg
NP_001119586.1:p.Ser240Arg
NP_001119587.1:p.Ser108Arg
NP_001119588.1:p.Ser108Arg
NP_001119589.1:p.Ser108Arg
NP_001119590.1:p.Ser201Arg
NP_001263624.1:p.Ser201Arg
NP_001263625.1:p.Ser201Arg
NP_001263626.1:p.Ser81Arg
NP_001263627.1:p.Ser81Arg
NP_001263628.1:p.Ser81Arg
NP_001263689.1:p.Ser201Arg
NP_001263690.1:p.Ser201Arg
LRG_321t1:c.720T>G
LRG_321:g.18308T>G
LRG_321p1:p.Ser240Arg
NC_000017.10:g.7577561A>C
NM_000546.5:c.720T>G

Protein change:

S108R

Links:

dbSNP: rs764342812

NCBI 1000 Genomes Browser:

rs764342812

Molecular consequence:

NM_000546.6:c.720T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.720T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.720T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.720T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.324T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.324T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.324T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.603T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.603T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.603T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.243T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.243T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.243T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.603T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.603T>G - 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
SCV000629859	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12509279, 12826609, 15037740, 17401432, 23863845, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000629859

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

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

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

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

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000629859.4

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects TP53 function (PMID: 12509279, 12826609, 15037740, 17401432, 23863845, 29979965, 30224644). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 458559). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 240 of the TP53 protein (p.Ser240Arg).

#	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 8, 2024

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