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NM_000546.6(TP53):c.358A>G (p.Lys120Glu) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 27, 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:
RCV000696142.7

Allele description

NM_000546.6(TP53):c.358A>G (p.Lys120Glu)

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.358A>G (p.Lys120Glu)
Other names:
p.K120E:AAG>GAG
HGVS:
  • NC_000017.11:g.7676011T>C
  • NG_017013.2:g.16540A>G
  • NM_000546.6:c.358A>GMANE SELECT
  • NM_001126112.3:c.358A>G
  • NM_001126113.3:c.358A>G
  • NM_001126114.3:c.358A>G
  • NM_001126118.2:c.241A>G
  • NM_001276695.3:c.241A>G
  • NM_001276696.3:c.241A>G
  • NM_001276760.3:c.241A>G
  • NM_001276761.3:c.241A>G
  • NP_000537.3:p.Lys120Glu
  • NP_000537.3:p.Lys120Glu
  • NP_001119584.1:p.Lys120Glu
  • NP_001119585.1:p.Lys120Glu
  • NP_001119586.1:p.Lys120Glu
  • NP_001119590.1:p.Lys81Glu
  • NP_001263624.1:p.Lys81Glu
  • NP_001263625.1:p.Lys81Glu
  • NP_001263689.1:p.Lys81Glu
  • NP_001263690.1:p.Lys81Glu
  • LRG_321t1:c.358A>G
  • LRG_321:g.16540A>G
  • LRG_321p1:p.Lys120Glu
  • NC_000017.10:g.7579329T>C
  • NM_000546.4:c.358A>G
  • NM_000546.5:c.358A>G
  • P04637:p.Lys120Glu
  • p.K120E
Protein change:
K120E
Links:
UniProtKB: P04637#VAR_044699; dbSNP: rs121912658
NCBI 1000 Genomes Browser:
rs121912658
Molecular consequence:
  • NM_000546.6:c.358A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.358A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.358A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.358A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.241A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.241A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.241A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.241A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.241A>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000824690Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 27, 2023) 		germlineclinical testing

PubMed (5)
[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

Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in Patients With Osteosarcoma.

Mirabello L, Zhu B, Koster R, Karlins E, Dean M, Yeager M, Gianferante M, Spector LG, Morton LM, Karyadi D, Robison LL, Armstrong GT, Bhatia S, Song L, Pankratz N, Pinheiro M, Gastier-Foster JM, Gorlick R, de Toledo SRC, Petrilli AS, Patino-Garcia A, Lecanda F, et al.

JAMA Oncol. 2020 May 1;6(5):724-734. doi: 10.1001/jamaoncol.2020.0197.

PubMed [citation]
PMID:
32191290
PMCID:
PMC7082769

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 (5)

Details of each submission

From Invitae, SCV000824690.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 120 of the TP53 protein (p.Lys120Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteosarcoma (PMID: 32191290). ClinVar contains an entry for this variant (Variation ID: 141098). 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 with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). 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.

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

Last Updated: Jul 15, 2024