NM_000546.6(TP53):c.514G>A (p.Val172Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 2019
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:: RCV001023618.3

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185524	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 22, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185524

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 22, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Details of each submission

From Ambry Genetics, SCV001185524.4

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

Description

The p.V172I variant (also known as c.514G>A), located in coding exon 4 of the TP53 gene, results from a G to A substitution at nucleotide position 514. The valine at codon 172 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was detected in a cohort of 8085 consecutive unselected Chinese breast cancer patients who underwent multi-gene panel testing (Sun J et al. Clin. Cancer Res. 2017 Oct;23(20):6113-6119). This variant was shown to have transactivation capabilities similar to wild type in yeast based functional studies (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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