NM_000546.6(TP53):c.631A>G (p.Thr211Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 29, 2023
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:: RCV004022604.1

Allele description [Variation Report for NM_000546.6(TP53):c.631A>G (p.Thr211Ala)]

NM_000546.6(TP53):c.631A>G (p.Thr211Ala)

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.631A>G (p.Thr211Ala)

HGVS:

NC_000017.11:g.7674900T>C
NG_017013.2:g.17651A>G
NM_000546.4:c.631A>G
NM_000546.6:c.631A>GMANE SELECT
NM_001126112.3:c.631A>G
NM_001126113.3:c.631A>G
NM_001126114.3:c.631A>G
NM_001126115.2:c.235A>G
NM_001126116.2:c.235A>G
NM_001126117.2:c.235A>G
NM_001126118.2:c.514A>G
NM_001276695.3:c.514A>G
NM_001276696.3:c.514A>G
NM_001276697.3:c.154A>G
NM_001276698.3:c.154A>G
NM_001276699.3:c.154A>G
NM_001276760.3:c.514A>G
NM_001276761.3:c.514A>G
NP_000537.3:p.Thr211Ala
NP_000537.3:p.Thr211Ala
NP_001119584.1:p.Thr211Ala
NP_001119585.1:p.Thr211Ala
NP_001119586.1:p.Thr211Ala
NP_001119587.1:p.Thr79Ala
NP_001119588.1:p.Thr79Ala
NP_001119589.1:p.Thr79Ala
NP_001119590.1:p.Thr172Ala
NP_001263624.1:p.Thr172Ala
NP_001263625.1:p.Thr172Ala
NP_001263626.1:p.Thr52Ala
NP_001263627.1:p.Thr52Ala
NP_001263628.1:p.Thr52Ala
NP_001263689.1:p.Thr172Ala
NP_001263690.1:p.Thr172Ala
LRG_321t1:c.631A>G
LRG_321:g.17651A>G
LRG_321p1:p.Thr211Ala
NC_000017.10:g.7578218T>C
NM_000546.5:c.631A>G

Protein change:

T172A

Links:

dbSNP: rs1060501198

NCBI 1000 Genomes Browser:

rs1060501198

Molecular consequence:

NM_000546.6:c.631A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.631A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.631A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.631A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.154A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.154A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.154A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.514A>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

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FGF1 fibroblast growth factor 1 [Homo sapiens]
FGF1 fibroblast growth factor 1 [Homo sapiens]
Gene ID:2246

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005036128	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 29979965, 30224644 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005036128

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 29, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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 (3)

Details of each submission

From Ambry Genetics, SCV005036128.1

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

Description

The p.T211A variant (also known as c.631A>G), located in coding exon 5 of the TP53 gene, results from an A to G substitution at nucleotide position 631. The threonine at codon 211 is replaced by alanine, an amino acid with similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has a dominant negative effect ([Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8;] Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

Last Updated: Sep 29, 2024

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