NM_000546.6(TP53):c.992A>G (p.Gln331Arg) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 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:: RCV001037256.10

Allele description [Variation Report for NM_000546.6(TP53):c.992A>G (p.Gln331Arg)]

NM_000546.6(TP53):c.992A>G (p.Gln331Arg)

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.992A>G (p.Gln331Arg)

HGVS:

NC_000017.11:g.7673536T>C
NG_017013.2:g.19015A>G
NM_000546.6:c.992A>GMANE SELECT
NM_001126112.3:c.992A>G
NM_001126113.3:c.992A>G
NM_001126114.3:c.992A>G
NM_001126115.2:c.596A>G
NM_001126116.2:c.596A>G
NM_001126117.2:c.596A>G
NM_001126118.2:c.875A>G
NM_001276695.3:c.875A>G
NM_001276696.3:c.875A>G
NM_001276697.3:c.515A>G
NM_001276698.3:c.515A>G
NM_001276699.3:c.515A>G
NM_001276760.3:c.875A>G
NM_001276761.3:c.875A>G
NP_000537.3:p.Gln331Arg
NP_000537.3:p.Gln331Arg
NP_001119584.1:p.Gln331Arg
NP_001119585.1:p.Gln331Arg
NP_001119586.1:p.Gln331Arg
NP_001119587.1:p.Gln199Arg
NP_001119588.1:p.Gln199Arg
NP_001119589.1:p.Gln199Arg
NP_001119590.1:p.Gln292Arg
NP_001263624.1:p.Gln292Arg
NP_001263625.1:p.Gln292Arg
NP_001263626.1:p.Gln172Arg
NP_001263627.1:p.Gln172Arg
NP_001263628.1:p.Gln172Arg
NP_001263689.1:p.Gln292Arg
NP_001263690.1:p.Gln292Arg
LRG_321t1:c.992A>G
LRG_321:g.19015A>G
LRG_321p1:p.Gln331Arg
NC_000017.10:g.7576854T>C
NM_000546.4:c.992A>G
NM_000546.5:c.992A>G

Protein change:

Q172R

Links:

dbSNP: rs1064795056

NCBI 1000 Genomes Browser:

rs1064795056

Molecular consequence:

NM_000546.6:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.875A>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
SCV001200660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12826609, 16007150, 19454241, 20978130, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 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

The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library.

Kawaguchi T, Kato S, Otsuka K, Watanabe G, Kumabe T, Tominaga T, Yoshimoto T, Ishioka C.

Oncogene. 2005 Oct 20;24(46):6976-81.

PubMed [citation]

PMID:: 16007150

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200660.5

#	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 glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 331 of the TP53 protein (p.Gln331Arg). 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: 421319). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 16007150, 19454241, 20978130). Studies have shown that this missense change is associated with inconclusive levels of altered splicing (Invitae). 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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