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NM_000546.6(TP53):c.536A>G (p.His179Arg) AND TP53-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 3, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003983035.2

Allele description [Variation Report for NM_000546.6(TP53):c.536A>G (p.His179Arg)]

NM_000546.6(TP53):c.536A>G (p.His179Arg)

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.536A>G (p.His179Arg)
HGVS:
  • NC_000017.11:g.7675076T>C
  • NG_017013.2:g.17475A>G
  • NM_000546.6:c.536A>GMANE SELECT
  • NM_001126112.3:c.536A>G
  • NM_001126113.3:c.536A>G
  • NM_001126114.3:c.536A>G
  • NM_001126115.2:c.140A>G
  • NM_001126116.2:c.140A>G
  • NM_001126117.2:c.140A>G
  • NM_001126118.2:c.419A>G
  • NM_001276695.3:c.419A>G
  • NM_001276696.3:c.419A>G
  • NM_001276697.3:c.59A>G
  • NM_001276698.3:c.59A>G
  • NM_001276699.3:c.59A>G
  • NM_001276760.3:c.419A>G
  • NM_001276761.3:c.419A>G
  • NP_000537.3:p.His179Arg
  • NP_000537.3:p.His179Arg
  • NP_001119584.1:p.His179Arg
  • NP_001119585.1:p.His179Arg
  • NP_001119586.1:p.His179Arg
  • NP_001119587.1:p.His47Arg
  • NP_001119588.1:p.His47Arg
  • NP_001119589.1:p.His47Arg
  • NP_001119590.1:p.His140Arg
  • NP_001263624.1:p.His140Arg
  • NP_001263625.1:p.His140Arg
  • NP_001263626.1:p.His20Arg
  • NP_001263627.1:p.His20Arg
  • NP_001263628.1:p.His20Arg
  • NP_001263689.1:p.His140Arg
  • NP_001263690.1:p.His140Arg
  • LRG_321t1:c.536A>G
  • LRG_321t3:c.536A>G
  • LRG_321:g.17475A>G
  • LRG_321p1:p.His179Arg
  • NC_000017.10:g.7578394T>C
  • NM_000546.4:c.536A>G
  • NM_000546.5:c.536A>G
Protein change:
H140R
Links:
dbSNP: rs1057519991
NCBI 1000 Genomes Browser:
rs1057519991
Molecular consequence:
  • NM_000546.6:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.140A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.140A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.140A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.59A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.59A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.59A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
TP53-related disorder
Synonyms:
TP53-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004800571PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(Jul 3, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004800571.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TP53 c.536A>G variant is predicted to result in the amino acid substitution p.His179Arg. This variant has been reported multiple times as a somatic variant, but it has also been detected in the germline of individuals with breast cancer and unspecified cancers (Supplementary Table 4, Mandelker et al. 2019. PubMed ID: 31050713; Kwong et al. 2020. PubMed ID: 33138793; Dong et al. 2011. PubMed ID: 21113594). It has also been detected in a control individual (Okawa et al. 2023. PubMed ID: 36243179). In vitro functional studies suggest this variant impacts protein function (see, for example, Kalo et al. 2007. PMID: 17875924; Hassan et al. 2008. PubMed ID: 18555592; Giacomelli et al. 2018 PubMed ID: 30224644). Alternative nucleotide substitutions affecting the same amino acid (p.His179Asp, p.His179Tyr, p.His179Gln) have been reported in individuals with breast cancer or Li-Fraumeni syndrome (Renaux-Petel et al. 2018. PubMed ID: 29070607; Brehin et al. 2018. PubMed ID: 28477316; Gonzalez et al. 2009. PubMed ID: 19556618). This variant is reported in 0.0099% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic or likely pathogenic by the majority of the submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/376606/). In summary, this variant is interpreted as likely pathogenic.

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

Last Updated: Nov 10, 2024