NM_000546.6(TP53):c.671A>G (p.Glu224Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 2, 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:: RCV001025571.3

Allele description [Variation Report for NM_000546.6(TP53):c.671A>G (p.Glu224Gly)]

NM_000546.6(TP53):c.671A>G (p.Glu224Gly)

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.671A>G (p.Glu224Gly)

HGVS:

NC_000017.11:g.7674860T>C
NG_017013.2:g.17691A>G
NM_000546.6:c.671A>GMANE SELECT
NM_001126112.3:c.671A>G
NM_001126113.3:c.671A>G
NM_001126114.3:c.671A>G
NM_001126115.2:c.275A>G
NM_001126116.2:c.275A>G
NM_001126117.2:c.275A>G
NM_001126118.2:c.554A>G
NM_001276695.3:c.554A>G
NM_001276696.3:c.554A>G
NM_001276697.3:c.194A>G
NM_001276698.3:c.194A>G
NM_001276699.3:c.194A>G
NM_001276760.3:c.554A>G
NM_001276761.3:c.554A>G
NP_000537.3:p.Glu224Gly
NP_001119584.1:p.Glu224Gly
NP_001119585.1:p.Glu224Gly
NP_001119586.1:p.Glu224Gly
NP_001119587.1:p.Glu92Gly
NP_001119588.1:p.Glu92Gly
NP_001119589.1:p.Glu92Gly
NP_001119590.1:p.Glu185Gly
NP_001263624.1:p.Glu185Gly
NP_001263625.1:p.Glu185Gly
NP_001263626.1:p.Glu65Gly
NP_001263627.1:p.Glu65Gly
NP_001263628.1:p.Glu65Gly
NP_001263689.1:p.Glu185Gly
NP_001263690.1:p.Glu185Gly
LRG_321:g.17691A>G
NC_000017.10:g.7578178T>C
NM_000546.4:c.671A>G

Protein change:

E185G

Links:

dbSNP: rs1131691028

NCBI 1000 Genomes Browser:

rs1131691028

Molecular consequence:

NM_000546.6:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.275A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.275A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.275A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.554A>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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RecName: Full=Protein phosphatase 1A; AltName: Full=Protein phosphatase 2C isofo...
RecName: Full=Protein phosphatase 1A; AltName: Full=Protein phosphatase 2C isoform alpha; Short=PP2C-alpha; AltName: Full=Protein phosphatase IA
gi|548442|sp|P35813.1|PPM1A_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001187784	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 2, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001187784

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 2, 2019)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV001187784.4

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

Description

The p.E224G variant (also known as c.671A>G), located in coding exon 5 of the TP53 gene, results from an A to G substitution at nucleotide position 671. The glutamic acid at codon 224 is replaced by glycine, an amino acid with similar properties. This variant was shown to have transactivation capabilities similar to wild type in yeast based functional studies (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (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 not well 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: May 1, 2024

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