NM_000546.6(TP53):c.698A>G (p.His233Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jun 18, 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:: RCV000569303.7

Allele description [Variation Report for NM_000546.6(TP53):c.698A>G (p.His233Arg)]

NM_000546.6(TP53):c.698A>G (p.His233Arg)

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.698A>G (p.His233Arg)

HGVS:

NC_000017.11:g.7674265T>C
NG_017013.2:g.18286A>G
NM_000546.6:c.698A>GMANE SELECT
NM_001126112.3:c.698A>G
NM_001126113.3:c.698A>G
NM_001126114.3:c.698A>G
NM_001126115.2:c.302A>G
NM_001126116.2:c.302A>G
NM_001126117.2:c.302A>G
NM_001126118.2:c.581A>G
NM_001276695.3:c.581A>G
NM_001276696.3:c.581A>G
NM_001276697.3:c.221A>G
NM_001276698.3:c.221A>G
NM_001276699.3:c.221A>G
NM_001276760.3:c.581A>G
NM_001276761.3:c.581A>G
NP_000537.3:p.His233Arg
NP_001119584.1:p.His233Arg
NP_001119585.1:p.His233Arg
NP_001119586.1:p.His233Arg
NP_001119587.1:p.His101Arg
NP_001119588.1:p.His101Arg
NP_001119589.1:p.His101Arg
NP_001119590.1:p.His194Arg
NP_001263624.1:p.His194Arg
NP_001263625.1:p.His194Arg
NP_001263626.1:p.His74Arg
NP_001263627.1:p.His74Arg
NP_001263628.1:p.His74Arg
NP_001263689.1:p.His194Arg
NP_001263690.1:p.His194Arg
LRG_321:g.18286A>G
NC_000017.10:g.7577583T>C
NM_000546.4:c.698A>G
P04637:p.His233Arg

Protein change:

H101R

Links:

UniProtKB: P04637#VAR_047181; dbSNP: rs879254233

NCBI 1000 Genomes Browser:

rs879254233

Molecular consequence:

NM_000546.6:c.698A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.698A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.698A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.698A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.302A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.302A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.302A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.221A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.221A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.221A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.581A>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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000667214	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 17, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 29979965, 30224644 Citation Link,
SCV002582017	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000667214

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Sep 17, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV002582017

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013..

PubMed [citation]

PMID:: 29979965

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000667214.5

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

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.

#	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

From Genome-Nilou Lab, SCV002582017.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 16, 2025

ClinVar

Relating variation to medicine