NM_000546.6(TP53):c.40C>G (p.Leu14Val) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 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:: RCV000699996.8

Allele description [Variation Report for NM_000546.6(TP53):c.40C>G (p.Leu14Val)]

NM_000546.6(TP53):c.40C>G (p.Leu14Val)

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.40C>G (p.Leu14Val)

HGVS:

NC_000017.11:g.7676555G>C
NG_017013.2:g.15996C>G
NM_000546.6:c.40C>GMANE SELECT
NM_001126112.3:c.40C>G
NM_001126113.3:c.40C>G
NM_001126114.3:c.40C>G
NM_001126118.2:c.-195C>G
NM_001276695.3:c.-78C>G
NM_001276696.3:c.-78C>G
NM_001276760.3:c.-78C>G
NM_001276761.3:c.-78C>G
NP_000537.3:p.Leu14Val
NP_000537.3:p.Leu14Val
NP_001119584.1:p.Leu14Val
NP_001119585.1:p.Leu14Val
NP_001119586.1:p.Leu14Val
LRG_321t1:c.40C>G
LRG_321:g.15996C>G
LRG_321p1:p.Leu14Val
NC_000017.10:g.7579873G>C
NM_000546.5:c.40C>G

Protein change:

L14V

Links:

dbSNP: rs1567558112

NCBI 1000 Genomes Browser:

rs1567558112

Molecular consequence:

NM_001126118.2:c.-195C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-78C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-78C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-78C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-78C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.40C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.40C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.40C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.40C>G - 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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Pathogen: clinical or host-associated sample from Klebsiella pneumoniae
Pathogen: clinical or host-associated sample from Klebsiella pneumoniae

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828730	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 16, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828730

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 16, 2018)

germline

clinical testing

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828730.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant has not been reported in the literature in individuals with TP53-related disease. This sequence change replaces leucine with valine at codon 14 of the TP53 protein (p.Leu14Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Nov 10, 2024

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