NM_000546.6(TP53):c.388C>T (p.Leu130Phe) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 7, 2023
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:: RCV000200055.9

Allele description [Variation Report for NM_000546.6(TP53):c.388C>T (p.Leu130Phe)]

NM_000546.6(TP53):c.388C>T (p.Leu130Phe)

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.388C>T (p.Leu130Phe)

HGVS:

NC_000017.11:g.7675224G>A
NG_017013.2:g.17327C>T
NM_000546.6:c.388C>TMANE SELECT
NM_001126112.3:c.388C>T
NM_001126113.3:c.388C>T
NM_001126114.3:c.388C>T
NM_001126115.2:c.-9C>T
NM_001126116.2:c.-9C>T
NM_001126117.2:c.-9C>T
NM_001126118.2:c.271C>T
NM_001276695.3:c.271C>T
NM_001276696.3:c.271C>T
NM_001276697.3:c.-90C>T
NM_001276698.3:c.-90C>T
NM_001276699.3:c.-90C>T
NM_001276760.3:c.271C>T
NM_001276761.3:c.271C>T
NP_000537.3:p.Leu130Phe
NP_000537.3:p.Leu130Phe
NP_001119584.1:p.Leu130Phe
NP_001119585.1:p.Leu130Phe
NP_001119586.1:p.Leu130Phe
NP_001119590.1:p.Leu91Phe
NP_001263624.1:p.Leu91Phe
NP_001263625.1:p.Leu91Phe
NP_001263689.1:p.Leu91Phe
NP_001263690.1:p.Leu91Phe
LRG_321t1:c.388C>T
LRG_321:g.17327C>T
LRG_321p1:p.Leu130Phe
NC_000017.10:g.7578542G>A
NM_000546.4:c.388C>T
NM_000546.5:c.388C>T
P04637:p.Leu130Phe

Protein change:

L130F

Links:

UniProtKB: P04637#VAR_044730; dbSNP: rs863224683

NCBI 1000 Genomes Browser:

rs863224683

Molecular consequence:

NM_001126115.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.271C>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
SCV000254631	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 7, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 11332399, 18511570, 19468865, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000254631

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 7, 2023)

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

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

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000254631.7

#	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 have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 216466). This missense change has been observed in individual(s) with Li-Fraumeni syndrome and/or breast cancer (PMID: 11332399, 18511570, 19468865). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 130 of the TP53 protein (p.Leu130Phe).

#	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 7, 2024

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Relating variation to medicine