NM_000546.6(TP53):c.644G>T (p.Ser215Ile) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 10, 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:: RCV003509529.2

Allele description [Variation Report for NM_000546.6(TP53):c.644G>T (p.Ser215Ile)]

NM_000546.6(TP53):c.644G>T (p.Ser215Ile)

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.644G>T (p.Ser215Ile)

HGVS:

NC_000017.11:g.7674887C>A
NG_017013.2:g.17664G>T
NM_000546.6:c.644G>TMANE SELECT
NM_001126112.3:c.644G>T
NM_001126113.3:c.644G>T
NM_001126114.3:c.644G>T
NM_001126115.2:c.248G>T
NM_001126116.2:c.248G>T
NM_001126117.2:c.248G>T
NM_001126118.2:c.527G>T
NM_001276695.3:c.527G>T
NM_001276696.3:c.527G>T
NM_001276697.3:c.167G>T
NM_001276698.3:c.167G>T
NM_001276699.3:c.167G>T
NM_001276760.3:c.527G>T
NM_001276761.3:c.527G>T
NP_000537.3:p.Ser215Ile
NP_000537.3:p.Ser215Ile
NP_001119584.1:p.Ser215Ile
NP_001119585.1:p.Ser215Ile
NP_001119586.1:p.Ser215Ile
NP_001119587.1:p.Ser83Ile
NP_001119588.1:p.Ser83Ile
NP_001119589.1:p.Ser83Ile
NP_001119590.1:p.Ser176Ile
NP_001263624.1:p.Ser176Ile
NP_001263625.1:p.Ser176Ile
NP_001263626.1:p.Ser56Ile
NP_001263627.1:p.Ser56Ile
NP_001263628.1:p.Ser56Ile
NP_001263689.1:p.Ser176Ile
NP_001263690.1:p.Ser176Ile
LRG_321t1:c.644G>T
LRG_321:g.17664G>T
LRG_321p1:p.Ser215Ile
NC_000017.10:g.7578205C>A
NM_000546.4:c.644G>T
NM_000546.5:c.644G>T

Protein change:

S176I

Links:

dbSNP: rs587782177

NCBI 1000 Genomes Browser:

rs587782177

Molecular consequence:

NM_000546.6:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.248G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.248G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.248G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.167G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.167G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.167G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.527G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.527G>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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OGT O-linked N-acetylglucosamine (GlcNAc) transferase [Homo sapiens]
OGT O-linked N-acetylglucosamine (GlcNAc) transferase [Homo sapiens]
Gene ID:8473

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004305354	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 10, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 21232794, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004305354

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 10, 2023)

germline

clinical testing

PubMed (5)
[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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004305354.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 215 of the TP53 protein (p.Ser215Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376660). 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 with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 21232794). 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: Sep 29, 2024

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