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NM_000546.6(TP53):c.734G>T (p.Gly245Val) AND Li-Fraumeni syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 16, 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:
RCV000558455.11

Allele description [Variation Report for NM_000546.6(TP53):c.734G>T (p.Gly245Val)]

NM_000546.6(TP53):c.734G>T (p.Gly245Val)

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.734G>T (p.Gly245Val)
HGVS:
  • NC_000017.11:g.7674229C>A
  • NG_017013.2:g.18322G>T
  • NM_000546.6:c.734G>TMANE SELECT
  • NM_001126112.3:c.734G>T
  • NM_001126113.3:c.734G>T
  • NM_001126114.3:c.734G>T
  • NM_001126115.2:c.338G>T
  • NM_001126116.2:c.338G>T
  • NM_001126117.2:c.338G>T
  • NM_001126118.2:c.617G>T
  • NM_001276695.3:c.617G>T
  • NM_001276696.3:c.617G>T
  • NM_001276697.3:c.257G>T
  • NM_001276698.3:c.257G>T
  • NM_001276699.3:c.257G>T
  • NM_001276760.3:c.617G>T
  • NM_001276761.3:c.617G>T
  • NP_000537.3:p.Gly245Val
  • NP_000537.3:p.Gly245Val
  • NP_001119584.1:p.Gly245Val
  • NP_001119585.1:p.Gly245Val
  • NP_001119586.1:p.Gly245Val
  • NP_001119587.1:p.Gly113Val
  • NP_001119588.1:p.Gly113Val
  • NP_001119589.1:p.Gly113Val
  • NP_001119590.1:p.Gly206Val
  • NP_001263624.1:p.Gly206Val
  • NP_001263625.1:p.Gly206Val
  • NP_001263626.1:p.Gly86Val
  • NP_001263627.1:p.Gly86Val
  • NP_001263628.1:p.Gly86Val
  • NP_001263689.1:p.Gly206Val
  • NP_001263690.1:p.Gly206Val
  • LRG_321t1:c.734G>T
  • LRG_321:g.18322G>T
  • LRG_321p1:p.Gly245Val
  • NC_000017.10:g.7577547C>A
  • NM_000546.4:c.734G>T
  • NM_000546.5:c.734G>T
Protein change:
G113V
Links:
dbSNP: rs121912656
NCBI 1000 Genomes Browser:
rs121912656
Molecular consequence:
  • NM_000546.6:c.734G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.734G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.734G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.734G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.338G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.338G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.338G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.617G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.617G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.617G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.257G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.257G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.257G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.617G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.617G>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000629863Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 16, 2021) 		germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma.

Toguchida J, Yamaguchi T, Dayton SH, Beauchamp RL, Herrera GE, Ishizaki K, Yamamuro T, Meyers PA, Little JB, Sasaki MS, et al.

N Engl J Med. 1992 May 14;326(20):1301-8.

PubMed [citation]
PMID:
1565143

Li-Fraumeni and Li-Fraumeni-like syndrome among children diagnosed with pediatric cancer in Southern Brazil.

Giacomazzi J, Selistre SG, Rossi C, Alemar B, Santos-Silva P, Pereira FS, Netto CB, Cossio SL, Roth DE, Brunetto AL, Zagonel-Oliveira M, Martel-Planche G, Goldim JR, Hainaut P, Camey SA, Ashton-Prolla P.

Cancer. 2013 Dec 15;119(24):4341-9. doi: 10.1002/cncr.28346. Epub 2013 Oct 7.

PubMed [citation]
PMID:
24122735
See all PubMed Citations (13)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000629863.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

For these reasons, this variant has been classified as Pathogenic. Different missense substitutions at this codon (p.Gly245Asp and p.Gly245Ser) have been determined to be pathogenic (PMID: 1565143, 24122735, 17311302, 12826609,20128691, 21343334, 25119136, 2259385), further suggesting that the glycine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense change disrupts the ability of TP53 to bind to DNA and significantly decreases its transcriptional transactivation activity (PMID: 12826609, 17606709). This variant has been reported in the literature in individuals with lung cancer, follicular lymphoma, and Li-Fraumeni associated cancers (PMID: 11180592, 11920788, 18628487, 17606709, Invitae). ClinVar contains an entry for this variant (Variation ID: 376603). This variant is present in population databases (rs121912656, ExAC 0.01%). This sequence change replaces glycine with valine at codon 245 of the TP53 protein (p.Gly245Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024