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NM_000546.6(TP53):c.344A>G (p.His115Arg) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 30, 2019
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:
RCV001192619.3

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)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001360869Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Jan 30, 2019) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.

de Andrade KC, Mirabello L, Stewart DR, Karlins E, Koster R, Wang M, Gapstur SM, Gaudet MM, Freedman ND, Landi MT, Lemonnier N, Hainaut P, Savage SA, Achatz MI.

Hum Mutat. 2017 Dec;38(12):1723-1730. doi: 10.1002/humu.23320. Epub 2017 Sep 21.

PubMed [citation]
PMID:
28861920
PMCID:
PMC6858060
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360869.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: The variant, TP53 c.344A>G (p.His115Arg) results in a non-conservative amino acid change located in the DNA-binding domain (IPR011615) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245988 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.344A>G in individuals affected with Li-Fraumeni Syndrome or related tumor phenotypes has been reported. Publications reported experimental evidence evaluating an impact on protein function, where one study demonstrated that the variant, p.H115R, does not affect the transactivation activity on eight different promoter elements (including p21) (data taken from the IARC Database, reference: Kato 2003), while another study demonstrated that the variant protein has a decreased oligonucleotide binding activity in an EMSA assay (where the probe contained the p53 response element from the p21 promoter) (Zupnick 2006). These data does not allow unequivocal conclusions about the variant effect. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Nov 10, 2024