NM_000546.6(TP53):c.656C>G (p.Pro219Arg) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 2020
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:: RCV001225718.8

Allele description [Variation Report for NM_000546.6(TP53):c.656C>G (p.Pro219Arg)]

NM_000546.6(TP53):c.656C>G (p.Pro219Arg)

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.656C>G (p.Pro219Arg)

HGVS:

NC_000017.11:g.7674875G>C
NG_017013.2:g.17676C>G
NM_000546.6:c.656C>GMANE SELECT
NM_001126112.3:c.656C>G
NM_001126113.3:c.656C>G
NM_001126114.3:c.656C>G
NM_001126115.2:c.260C>G
NM_001126116.2:c.260C>G
NM_001126117.2:c.260C>G
NM_001126118.2:c.539C>G
NM_001276695.3:c.539C>G
NM_001276696.3:c.539C>G
NM_001276697.3:c.179C>G
NM_001276698.3:c.179C>G
NM_001276699.3:c.179C>G
NM_001276760.3:c.539C>G
NM_001276761.3:c.539C>G
NP_000537.3:p.Pro219Arg
NP_001119584.1:p.Pro219Arg
NP_001119585.1:p.Pro219Arg
NP_001119586.1:p.Pro219Arg
NP_001119587.1:p.Pro87Arg
NP_001119588.1:p.Pro87Arg
NP_001119589.1:p.Pro87Arg
NP_001119590.1:p.Pro180Arg
NP_001263624.1:p.Pro180Arg
NP_001263625.1:p.Pro180Arg
NP_001263626.1:p.Pro60Arg
NP_001263627.1:p.Pro60Arg
NP_001263628.1:p.Pro60Arg
NP_001263689.1:p.Pro180Arg
NP_001263690.1:p.Pro180Arg
LRG_321t1:c.656C>G
LRG_321:g.17676C>G
NC_000017.10:g.7578193G>C
NM_000546.5:c.656C>G

Protein change:

P180R

Links:

dbSNP: rs1420675064

NCBI 1000 Genomes Browser:

rs1420675064

Molecular consequence:

NM_000546.6:c.656C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.656C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.656C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.656C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.260C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.260C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.260C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.179C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.179C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.179C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

Recent activity

Clear Turn Off Turn On

Poecilia formosa, whole genome shotgun sequence
Poecilia formosa, whole genome shotgun sequence
gi|553116626|gb|AYCK01010146.1||gnl AYCK01|Poecilia_formosa-5.1.2-159.16

Nucleotide
Scaphyglottis cf. pulchella DB 2965 maturase K (matK) gene, partial cds; chlorop...
Scaphyglottis cf. pulchella DB 2965 maturase K (matK) gene, partial cds; chloroplast
gi|167889894|gb|EU214524.1|

Nucleotide
Scaphyglottis punctulata voucher MW 102 maturase K (matK) gene, partial cds; chl...
Scaphyglottis punctulata voucher MW 102 maturase K (matK) gene, partial cds; chloroplast
gi|167889900|gb|EU214527.1|

Nucleotide

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
SCV001398006	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 8, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25925845, 25584008, 7966399, 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001398006

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 8, 2020)

germline

clinical testing

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

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

Germline TP53 mutational spectrum in French Canadians with breast cancer.

Arcand SL, Akbari MR, Mes-Masson AM, Provencher D, Foulkes WD, Narod SA, Tonin PN.

BMC Med Genet. 2015 Apr 12;16:24. doi: 10.1186/s12881-015-0169-y.

PubMed [citation]

PMID:: 25925845
PMCID:: PMC4436120

Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study.

Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, Malkin D.

J Clin Oncol. 2015 Feb 20;33(6):602-9. doi: 10.1200/JCO.2013.52.6863. Epub 2015 Jan 12.

PubMed [citation]

PMID:: 25584008
PMCID:: PMC4517369

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001398006.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro219 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25925845, 25584008, 7966399, 12826609). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to affect TP53 protein function (PMID: 12826609). This variant has not been reported in the literature in individuals with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 219 of the TP53 protein (p.Pro219Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.

#	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

ClinVar

Relating variation to medicine