U.S. flag

An official website of the United States government

  • delete

NM_000546.6(TP53):c.1066G>C (p.Gly356Arg) AND Li-Fraumeni syndrome 1

Germline classification:
Likely benign (1 submission)
Last evaluated:
Aug 4, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001723809.3

Allele description

NM_000546.6(TP53):c.1066G>C (p.Gly356Arg)

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.1066G>C (p.Gly356Arg)
Other names:
NM_000546.5(TP53):c.1066G>C; p.Gly356Arg
HGVS:
  • NC_000017.11:g.7670643C>G
  • NG_017013.2:g.21908G>C
  • NM_000546.6:c.1066G>CMANE SELECT
  • NM_001126112.3:c.1066G>C
  • NM_001126113.3:c.*85G>C
  • NM_001126114.3:c.*173G>C
  • NM_001126115.2:c.670G>C
  • NM_001126116.2:c.*173G>C
  • NM_001126117.2:c.*85G>C
  • NM_001126118.2:c.949G>C
  • NM_001276695.3:c.*85G>C
  • NM_001276696.3:c.*173G>C
  • NM_001276697.3:c.589G>C
  • NM_001276698.3:c.*173G>C
  • NM_001276699.3:c.*85G>C
  • NM_001276760.3:c.949G>C
  • NM_001276761.3:c.949G>C
  • NP_000537.3:p.Gly356Arg
  • NP_000537.3:p.Gly356Arg
  • NP_001119584.1:p.Gly356Arg
  • NP_001119587.1:p.Gly224Arg
  • NP_001119590.1:p.Gly317Arg
  • NP_001263626.1:p.Gly197Arg
  • NP_001263689.1:p.Gly317Arg
  • NP_001263690.1:p.Gly317Arg
  • LRG_321t1:c.1066G>C
  • LRG_321:g.21908G>C
  • LRG_321p1:p.Gly356Arg
  • NC_000017.10:g.7573961C>G
  • NM_000546.4:c.1066G>C
  • NM_000546.5:c.1066G>C
Protein change:
G197R
Links:
dbSNP: rs766786605
NCBI 1000 Genomes Browser:
rs766786605
Molecular consequence:
  • NM_001126113.3:c.*85G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126114.3:c.*173G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126116.2:c.*173G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126117.2:c.*85G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276695.3:c.*85G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276696.3:c.*173G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276698.3:c.*173G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276699.3:c.*85G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000546.6:c.1066G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.1066G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.670G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.949G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.949G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.949G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Identifiers:
Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001949906ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1.2)		Likely benign
(Aug 4, 2021) 		germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

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

Details of each submission

From ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001949906.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

Transactivation assays show [retained/supertransactivation] function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributor). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.1066G>C (p.Gly356Arg) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3_BS2_Supporting, BP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024