NM_000546.6(TP53):c.989T>A (p.Leu330His) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 5, 2021
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:: RCV001913648.4

Allele description [Variation Report for NM_000546.6(TP53):c.989T>A (p.Leu330His)]

NM_000546.6(TP53):c.989T>A (p.Leu330His)

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>A (p.Leu330His)

HGVS:

NC_000017.11:g.7673539A>T
NG_017013.2:g.19012T>A
NM_000546.6:c.989T>AMANE SELECT
NM_001126112.3:c.989T>A
NM_001126113.3:c.989T>A
NM_001126114.3:c.989T>A
NM_001126115.2:c.593T>A
NM_001126116.2:c.593T>A
NM_001126117.2:c.593T>A
NM_001126118.2:c.872T>A
NM_001276695.3:c.872T>A
NM_001276696.3:c.872T>A
NM_001276697.3:c.512T>A
NM_001276698.3:c.512T>A
NM_001276699.3:c.512T>A
NM_001276760.3:c.872T>A
NM_001276761.3:c.872T>A
NP_000537.3:p.Leu330His
NP_001119584.1:p.Leu330His
NP_001119585.1:p.Leu330His
NP_001119586.1:p.Leu330His
NP_001119587.1:p.Leu198His
NP_001119588.1:p.Leu198His
NP_001119589.1:p.Leu198His
NP_001119590.1:p.Leu291His
NP_001263624.1:p.Leu291His
NP_001263625.1:p.Leu291His
NP_001263626.1:p.Leu171His
NP_001263627.1:p.Leu171His
NP_001263628.1:p.Leu171His
NP_001263689.1:p.Leu291His
NP_001263690.1:p.Leu291His
LRG_321:g.19012T>A
NC_000017.10:g.7576857A>T

Protein change:

L171H

Links:

dbSNP: rs1597359140

NCBI 1000 Genomes Browser:

rs1597359140

Molecular consequence:

NM_000546.6:c.989T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.989T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.989T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.989T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.872T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.872T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.872T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.512T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.512T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.512T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.872T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.872T>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
SCV002184060	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 5, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9766574, 10653977, 12826609, 19454241, 20978130, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002184060

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 5, 2021)

germline

clinical testing

PubMed (7)
[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

Characterization of p53 mutants identified in human tumors with a missense mutation in the tetramerization domain.

Rollenhagen C, Chène P.

Int J Cancer. 1998 Oct 29;78(3):372-6.

PubMed [citation]

PMID:: 9766574

Function, oligomerization, and conformation of tumor-associated p53 proteins with mutated C-terminus.

Atz J, Wagner P, Roemer K.

J Cell Biochem. 2000 Jan;76(4):572-84.

PubMed [citation]

PMID:: 10653977

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002184060.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

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 are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 protein function (PMID: 9766574, 10653977, 12826609, 19454241, 20978130, 30224644). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with histidine at codon 330 of the TP53 protein (p.Leu330His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine.

#	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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