NM_000546.6(TP53):c.989T>C (p.Leu330Pro) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 9, 2018
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:: RCV000806974.6

Allele description [Variation Report for NM_000546.6(TP53):c.989T>C (p.Leu330Pro)]

NM_000546.6(TP53):c.989T>C (p.Leu330Pro)

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.989T>C (p.Leu330Pro)

HGVS:

NC_000017.11:g.7673539A>G
NG_017013.2:g.19012T>C
NM_000546.6:c.989T>CMANE SELECT
NM_001126112.3:c.989T>C
NM_001126113.3:c.989T>C
NM_001126114.3:c.989T>C
NM_001126115.2:c.593T>C
NM_001126116.2:c.593T>C
NM_001126117.2:c.593T>C
NM_001126118.2:c.872T>C
NM_001276695.3:c.872T>C
NM_001276696.3:c.872T>C
NM_001276697.3:c.512T>C
NM_001276698.3:c.512T>C
NM_001276699.3:c.512T>C
NM_001276760.3:c.872T>C
NM_001276761.3:c.872T>C
NP_000537.3:p.Leu330Pro
NP_000537.3:p.Leu330Pro
NP_001119584.1:p.Leu330Pro
NP_001119585.1:p.Leu330Pro
NP_001119586.1:p.Leu330Pro
NP_001119587.1:p.Leu198Pro
NP_001119588.1:p.Leu198Pro
NP_001119589.1:p.Leu198Pro
NP_001119590.1:p.Leu291Pro
NP_001263624.1:p.Leu291Pro
NP_001263625.1:p.Leu291Pro
NP_001263626.1:p.Leu171Pro
NP_001263627.1:p.Leu171Pro
NP_001263628.1:p.Leu171Pro
NP_001263689.1:p.Leu291Pro
NP_001263690.1:p.Leu291Pro
LRG_321t1:c.989T>C
LRG_321:g.19012T>C
LRG_321p1:p.Leu330Pro
NC_000017.10:g.7576857A>G
NM_000546.5:c.989T>C

Protein change:

L171P

Links:

dbSNP: rs1597359140

NCBI 1000 Genomes Browser:

rs1597359140

Molecular consequence:

NM_000546.6:c.989T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.989T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.989T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.989T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.593T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.593T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.593T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.872T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.872T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.872T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.512T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.512T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.512T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.872T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.872T>C - 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
SCV000946998	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 9, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 20978130, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000946998

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 9, 2018)

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

Cancer-associated p53 tetramerization domain mutants: quantitative analysis reveals a low threshold for tumor suppressor inactivation.

Kamada R, Nomura T, Anderson CW, Sakaguchi K.

J Biol Chem. 2011 Jan 7;286(1):252-8. doi: 10.1074/jbc.M110.174698. Epub 2010 Oct 26.

PubMed [citation]

PMID:: 20978130
PMCID:: PMC3012982

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000946998.4

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

Description

This sequence change replaces leucine with proline at codon 330 of the TP53 protein (p.Leu330Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). 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 variant interferes with the stability and impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609, 20978130). This variant has not been reported in the literature in individuals with TP53-related disease.

#	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: Feb 20, 2024

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