NM_000546.6(TP53):c.263C>T (p.Ala88Val) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 2020
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:: RCV001322778.8

Allele description [Variation Report for NM_000546.6(TP53):c.263C>T (p.Ala88Val)]

NM_000546.6(TP53):c.263C>T (p.Ala88Val)

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.263C>T (p.Ala88Val)

HGVS:

NC_000017.11:g.7676106G>A
NG_017013.2:g.16445C>T
NM_000546.6:c.263C>TMANE SELECT
NM_001126112.3:c.263C>T
NM_001126113.3:c.263C>T
NM_001126114.3:c.263C>T
NM_001126118.2:c.146C>T
NM_001276695.3:c.146C>T
NM_001276696.3:c.146C>T
NM_001276760.3:c.146C>T
NM_001276761.3:c.146C>T
NP_000537.3:p.Ala88Val
NP_001119584.1:p.Ala88Val
NP_001119585.1:p.Ala88Val
NP_001119586.1:p.Ala88Val
NP_001119590.1:p.Ala49Val
NP_001263624.1:p.Ala49Val
NP_001263625.1:p.Ala49Val
NP_001263689.1:p.Ala49Val
NP_001263690.1:p.Ala49Val
LRG_321:g.16445C>T
NC_000017.10:g.7579424G>A
NM_000546.4:c.263C>T

Protein change:

A49V

Links:

dbSNP: rs1555526631

NCBI 1000 Genomes Browser:

rs1555526631

Molecular consequence:

NM_000546.6:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.146C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001513665	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 27, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001513665

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 27, 2020)

germline

clinical testing

PubMed (3)
[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

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]

PMID:: 30224644
PMCID:: PMC6168352

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001513665.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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 variant does not substantially affect TP53 protein function (PMID: 12826609, 30224644). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 480734). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 88 of the TP53 protein (p.Ala88Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine.

#	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: Nov 10, 2024

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