NM_000546.6(TP53):c.991C>G (p.Gln331Glu) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 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:: RCV002681435.3

Allele description [Variation Report for NM_000546.6(TP53):c.991C>G (p.Gln331Glu)]

NM_000546.6(TP53):c.991C>G (p.Gln331Glu)

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.991C>G (p.Gln331Glu)

HGVS:

NC_000017.11:g.7673537G>C
NG_017013.2:g.19014C>G
NM_000546.6:c.991C>GMANE SELECT
NM_001126112.3:c.991C>G
NM_001126113.3:c.991C>G
NM_001126114.3:c.991C>G
NM_001126115.2:c.595C>G
NM_001126116.2:c.595C>G
NM_001126117.2:c.595C>G
NM_001126118.2:c.874C>G
NM_001276695.3:c.874C>G
NM_001276696.3:c.874C>G
NM_001276697.3:c.514C>G
NM_001276698.3:c.514C>G
NM_001276699.3:c.514C>G
NM_001276760.3:c.874C>G
NM_001276761.3:c.874C>G
NM_001407262.1:c.991C>G
NM_001407263.1:c.874C>G
NM_001407264.1:c.991C>G
NM_001407265.1:c.874C>G
NM_001407266.1:c.991C>G
NM_001407267.1:c.874C>G
NM_001407268.1:c.991C>G
NM_001407269.1:c.874C>G
NM_001407270.1:c.991C>G
NM_001407271.1:c.874C>G
NP_000537.3:p.Gln331Glu
NP_000537.3:p.Gln331Glu
NP_001119584.1:p.Gln331Glu
NP_001119584.1:p.Gln331Glu
NP_001119585.1:p.Gln331Glu
NP_001119585.1:p.Gln331Glu
NP_001119586.1:p.Gln331Glu
NP_001119586.1:p.Gln331Glu
NP_001119587.1:p.Gln199Glu
NP_001119587.1:p.Gln199Glu
NP_001119588.1:p.Gln199Glu
NP_001119588.1:p.Gln199Glu
NP_001119589.1:p.Gln199Glu
NP_001119589.1:p.Gln199Glu
NP_001119590.1:p.Gln292Glu
NP_001119590.1:p.Gln292Glu
NP_001263624.1:p.Gln292Glu
NP_001263625.1:p.Gln292Glu
NP_001263626.1:p.Gln172Glu
NP_001263627.1:p.Gln172Glu
NP_001263628.1:p.Gln172Glu
NP_001263689.1:p.Gln292Glu
NP_001263690.1:p.Gln292Glu
NP_001394191.1:p.Gln331Glu
NP_001394192.1:p.Gln292Glu
NP_001394193.1:p.Gln331Glu
NP_001394194.1:p.Gln292Glu
NP_001394195.1:p.Gln331Glu
NP_001394196.1:p.Gln292Glu
NP_001394197.1:p.Gln331Glu
NP_001394198.1:p.Gln292Glu
NP_001394199.1:p.Gln331Glu
NP_001394200.1:p.Gln292Glu
LRG_321t1:c.991C>G
LRG_321t2:c.991C>G
LRG_321t3:c.991C>G
LRG_321t4:c.991C>G
LRG_321t5:c.595C>G
LRG_321t6:c.595C>G
LRG_321t7:c.595C>G
LRG_321t8:c.874C>G
LRG_321:g.19014C>G
LRG_321:p.Gln331Glu
LRG_321p1:p.Gln331Glu
LRG_321p3:p.Gln331Glu
LRG_321p4:p.Gln331Glu
LRG_321p5:p.Gln199Glu
LRG_321p6:p.Gln199Glu
LRG_321p7:p.Gln199Glu
LRG_321p8:p.Gln292Glu
NC_000017.10:g.7576855G>C
NM_000546.5:c.991C>G
NM_001126112.2:c.991C>G
NM_001126113.2:c.991C>G
NM_001126114.2:c.991C>G
NM_001126115.1:c.595C>G
NM_001126116.1:c.595C>G
NM_001126117.1:c.595C>G
NM_001126118.1:c.874C>G
NR_176326.1:n.1020C>G

Protein change:

Q172E

Molecular consequence:

NM_000546.6:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.595C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.595C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.595C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.514C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.514C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.514C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.874C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.874C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002991655	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 5, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002991655

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 5, 2021)

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

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]

PMID:: 30224644
PMCID:: PMC6168352

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002991655.2

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

Description

This variant has not been reported in the literature in individuals with TP53-related conditions. 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 variant does not substantially affect TP53 protein function (PMID: 12826609, 30224644). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 331 of the TP53 protein (p.Gln331Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid.

#	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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