NM_000546.6(TP53):c.653T>G (p.Val218Gly) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 30, 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:: RCV000633350.8

Allele description [Variation Report for NM_000546.6(TP53):c.653T>G (p.Val218Gly)]

NM_000546.6(TP53):c.653T>G (p.Val218Gly)

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.653T>G (p.Val218Gly)

HGVS:

NC_000017.11:g.7674878A>C
NG_017013.2:g.17673T>G
NM_000546.6:c.653T>GMANE SELECT
NM_001126112.3:c.653T>G
NM_001126113.3:c.653T>G
NM_001126114.3:c.653T>G
NM_001126115.2:c.257T>G
NM_001126116.2:c.257T>G
NM_001126117.2:c.257T>G
NM_001126118.2:c.536T>G
NM_001276695.3:c.536T>G
NM_001276696.3:c.536T>G
NM_001276697.3:c.176T>G
NM_001276698.3:c.176T>G
NM_001276699.3:c.176T>G
NM_001276760.3:c.536T>G
NM_001276761.3:c.536T>G
NP_000537.3:p.Val218Gly
NP_000537.3:p.Val218Gly
NP_001119584.1:p.Val218Gly
NP_001119585.1:p.Val218Gly
NP_001119586.1:p.Val218Gly
NP_001119587.1:p.Val86Gly
NP_001119588.1:p.Val86Gly
NP_001119589.1:p.Val86Gly
NP_001119590.1:p.Val179Gly
NP_001263624.1:p.Val179Gly
NP_001263625.1:p.Val179Gly
NP_001263626.1:p.Val59Gly
NP_001263627.1:p.Val59Gly
NP_001263628.1:p.Val59Gly
NP_001263689.1:p.Val179Gly
NP_001263690.1:p.Val179Gly
LRG_321t1:c.653T>G
LRG_321:g.17673T>G
LRG_321p1:p.Val218Gly
NC_000017.10:g.7578196A>C
NM_000546.5:c.653T>G

Protein change:

V179G

Links:

dbSNP: rs1555525743

NCBI 1000 Genomes Browser:

rs1555525743

Molecular consequence:

NM_000546.6:c.653T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.653T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.653T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.653T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.257T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.257T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.257T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.536T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.536T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.536T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.176T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.176T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.176T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.536T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.536T>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
SCV000754572	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 30, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 32817165, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754572

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 30, 2022)

germline

clinical testing

PubMed (5)
[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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754572.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 528249). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 32817165). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 218 of the TP53 protein (p.Val218Gly).

#	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: Sep 29, 2024

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