NM_000546.6(TP53):c.344A>G (p.His115Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Oct 24, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000575197.10

Allele description [Variation Report for NM_000546.6(TP53):c.344A>G (p.His115Arg)]

NM_000546.6(TP53):c.344A>G (p.His115Arg)

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.344A>G (p.His115Arg)
Other names:
p.H115R:CAT>CGT
HGVS:
  • NC_000017.11:g.7676025T>C
  • NG_017013.2:g.16526A>G
  • NM_000546.6:c.344A>GMANE SELECT
  • NM_001126112.3:c.344A>G
  • NM_001126113.3:c.344A>G
  • NM_001126114.3:c.344A>G
  • NM_001126118.2:c.227A>G
  • NM_001276695.3:c.227A>G
  • NM_001276696.3:c.227A>G
  • NM_001276760.3:c.227A>G
  • NM_001276761.3:c.227A>G
  • NP_000537.3:p.His115Arg
  • NP_000537.3:p.His115Arg
  • NP_001119584.1:p.His115Arg
  • NP_001119585.1:p.His115Arg
  • NP_001119586.1:p.His115Arg
  • NP_001119590.1:p.His76Arg
  • NP_001263624.1:p.His76Arg
  • NP_001263625.1:p.His76Arg
  • NP_001263689.1:p.His76Arg
  • NP_001263690.1:p.His76Arg
  • LRG_321t1:c.344A>G
  • LRG_321t2:c.344A>G
  • LRG_321:g.16526A>G
  • LRG_321p1:p.His115Arg
  • NC_000017.10:g.7579343T>C
  • NM_000546.4:c.344A>G
  • NM_000546.5:c.344A>G
  • NM_001126112.2(TP53):c.344A>G
  • p.His115Arg
Protein change:
H115R
Links:
dbSNP: rs730881996
NCBI 1000 Genomes Browser:
rs730881996
Molecular consequence:
  • NM_000546.6:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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
SCV000676296Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely benign
(Oct 24, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV001345638Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 4, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 analysis of the p53 core domain L1 loop.

Zupnick A, Prives C.

J Biol Chem. 2006 Jul 21;281(29):20464-73. Epub 2006 May 10.

PubMed [citation]
PMID:
16687402
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000676296.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

From Color Diagnostics, LLC DBA Color Health, SCV001345638.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This missense variant replaces histidine with arginine at codon 115 of the TP53 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have shown the mutant protein to exhibit normal transactivation activity in a yeast transactivation assay (PMID 12826609 and IARC database) and to be functional in human cell growth assays (PMID: 29979965, 30224644). The mutant protein has shown a partially reduced binding affinity for the p53 response element from the p21 promoter (PMID: 16687402). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 10, 2024