NM_000546.6(TP53):c.514G>A (p.Val172Ile) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 7, 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:: RCV003509649.1

Allele description [Variation Report for NM_000546.6(TP53):c.514G>A (p.Val172Ile)]

NM_000546.6(TP53):c.514G>A (p.Val172Ile)

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.514G>A (p.Val172Ile)

HGVS:

NC_000017.11:g.7675098C>T
NG_017013.2:g.17453G>A
NM_000546.6:c.514G>AMANE SELECT
NM_001126112.3:c.514G>A
NM_001126113.3:c.514G>A
NM_001126114.3:c.514G>A
NM_001126115.2:c.118G>A
NM_001126116.2:c.118G>A
NM_001126117.2:c.118G>A
NM_001126118.2:c.397G>A
NM_001276695.3:c.397G>A
NM_001276696.3:c.397G>A
NM_001276697.3:c.37G>A
NM_001276698.3:c.37G>A
NM_001276699.3:c.37G>A
NM_001276760.3:c.397G>A
NM_001276761.3:c.397G>A
NP_000537.3:p.Val172Ile
NP_001119584.1:p.Val172Ile
NP_001119585.1:p.Val172Ile
NP_001119586.1:p.Val172Ile
NP_001119587.1:p.Val40Ile
NP_001119588.1:p.Val40Ile
NP_001119589.1:p.Val40Ile
NP_001119590.1:p.Val133Ile
NP_001263624.1:p.Val133Ile
NP_001263625.1:p.Val133Ile
NP_001263626.1:p.Val13Ile
NP_001263627.1:p.Val13Ile
NP_001263628.1:p.Val13Ile
NP_001263689.1:p.Val133Ile
NP_001263690.1:p.Val133Ile
LRG_321:g.17453G>A
NC_000017.10:g.7578416C>T
NC_000017.10:g.7578416C>T
NM_000546.4:c.514G>A

Protein change:

V133I

Links:

dbSNP: rs1131691043

NCBI 1000 Genomes Browser:

rs1131691043

Molecular consequence:

NM_000546.6:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.397G>A - 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
SCV004296709	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28724667, 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296709

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 7, 2023)

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

Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.

Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, Wang L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y.

Clin Cancer Res. 2017 Oct 15;23(20):6113-6119. doi: 10.1158/1078-0432.CCR-16-3227. Epub 2017 Jul 19.

PubMed [citation]

PMID:: 28724667

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, SCV004296709.1

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 172 of the TP53 protein (p.Val172Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 825481). 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. 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: May 1, 2024

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