NM_000546.6(TP53):c.1081G>A (p.Gly361Arg) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 21, 2022
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:: RCV002720768.2

Allele description [Variation Report for NM_000546.6(TP53):c.1081G>A (p.Gly361Arg)]

NM_000546.6(TP53):c.1081G>A (p.Gly361Arg)

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.1081G>A (p.Gly361Arg)

HGVS:

NC_000017.11:g.7670628C>T
NG_017013.2:g.21923G>A
NM_000546.4:c.1081G>A
NM_000546.6:c.1081G>AMANE SELECT
NM_001126112.3:c.1081G>A
NM_001126113.3:c.*100G>A
NM_001126114.3:c.*188G>A
NM_001126115.2:c.685G>A
NM_001126116.2:c.*188G>A
NM_001126117.2:c.*100G>A
NM_001126118.2:c.964G>A
NM_001276695.3:c.*100G>A
NM_001276696.3:c.*188G>A
NM_001276697.3:c.604G>A
NM_001276698.3:c.*188G>A
NM_001276699.3:c.*100G>A
NM_001276760.3:c.964G>A
NM_001276761.3:c.964G>A
NM_001407262.1:c.1081G>A
NM_001407263.1:c.964G>A
NM_001407264.1:c.1081G>A
NM_001407265.1:c.964G>A
NM_001407266.1:c.1081G>A
NM_001407267.1:c.964G>A
NM_001407268.1:c.*188G>A
NM_001407269.1:c.*188G>A
NM_001407270.1:c.*188G>A
NM_001407271.1:c.*188G>A
NP_000537.3:p.Gly361Arg
NP_000537.3:p.Gly361Arg
NP_001119584.1:p.Gly361Arg
NP_001119584.1:p.Gly361Arg
NP_001119587.1:p.Gly229Arg
NP_001119587.1:p.Gly229Arg
NP_001119590.1:p.Gly322Arg
NP_001119590.1:p.Gly322Arg
NP_001263626.1:p.Gly202Arg
NP_001263689.1:p.Gly322Arg
NP_001263690.1:p.Gly322Arg
NP_001394191.1:p.Gly361Arg
NP_001394192.1:p.Gly322Arg
NP_001394193.1:p.Gly361Arg
NP_001394194.1:p.Gly322Arg
NP_001394195.1:p.Gly361Arg
NP_001394196.1:p.Gly322Arg
LRG_321t1:c.1081G>A
LRG_321t2:c.1081G>A
LRG_321t3:c.*188G>A
LRG_321t4:c.*100G>A
LRG_321t5:c.685G>A
LRG_321t6:c.*188G>A
LRG_321t7:c.*100G>A
LRG_321t8:c.964G>A
LRG_321:g.21923G>A
LRG_321:p.Gly361Arg
LRG_321p1:p.Gly361Arg
LRG_321p5:p.Gly229Arg
LRG_321p8:p.Gly322Arg
NC_000017.10:g.7573946C>T
NM_000546.5:c.1081G>A
NM_001126112.2:c.1081G>A
NM_001126113.2:c.*100G>A
NM_001126114.2:c.*188G>A
NM_001126115.1:c.685G>A
NM_001126116.1:c.*188G>A
NM_001126117.1:c.*100G>A
NM_001126118.1:c.964G>A
NR_176326.1:n.1110G>A

Protein change:

G202R

Molecular consequence:

NM_001126113.3:c.*100G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126114.3:c.*188G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126116.2:c.*188G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126117.2:c.*100G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276695.3:c.*100G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276696.3:c.*188G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276698.3:c.*188G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276699.3:c.*100G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000546.6:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.685G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.964G>A - 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

Recent activity

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Mus musculus tubulin, delta 1 (Tubd1), transcript variant 1, mRNA
Mus musculus tubulin, delta 1 (Tubd1), transcript variant 1, mRNA
gi|312261236|ref|NM_001199045.1|

Nucleotide
7-methylguanosine phosphate-specific 5'-nucleotidase isoform 3 [Mus musculus]
7-methylguanosine phosphate-specific 5'-nucleotidase isoform 3 [Mus musculus]
gi|1386806180|ref|NP_001349895.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003002291	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 21, 2022)	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

SCV003002291

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 21, 2022)

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 Invitae, SCV003002291.2

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

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 does not substantially affect TP53 function (PMID: 12826609, 30224644). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 361 of the TP53 protein (p.Gly361Arg).

#	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: Aug 11, 2024

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