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NM_000546.6(TP53):c.212C>G (p.Pro71Arg) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 13, 2017
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:
RCV000230713.9

Allele description [Variation Report for NM_000546.6(TP53):c.212C>G (p.Pro71Arg)]

NM_000546.6(TP53):c.212C>G (p.Pro71Arg)

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.212C>G (p.Pro71Arg)
HGVS:
  • NC_000017.11:g.7676157G>C
  • NG_017013.2:g.16394C>G
  • NM_000546.6:c.212C>GMANE SELECT
  • NM_001126112.3:c.212C>G
  • NM_001126113.3:c.212C>G
  • NM_001126114.3:c.212C>G
  • NM_001126118.2:c.95C>G
  • NM_001276695.3:c.95C>G
  • NM_001276696.3:c.95C>G
  • NM_001276760.3:c.95C>G
  • NM_001276761.3:c.95C>G
  • NP_000537.3:p.Pro71Arg
  • NP_000537.3:p.Pro71Arg
  • NP_001119584.1:p.Pro71Arg
  • NP_001119585.1:p.Pro71Arg
  • NP_001119586.1:p.Pro71Arg
  • NP_001119590.1:p.Pro32Arg
  • NP_001263624.1:p.Pro32Arg
  • NP_001263625.1:p.Pro32Arg
  • NP_001263689.1:p.Pro32Arg
  • NP_001263690.1:p.Pro32Arg
  • LRG_321t1:c.212C>G
  • LRG_321:g.16394C>G
  • LRG_321p1:p.Pro71Arg
  • NC_000017.10:g.7579475G>C
  • NM_000546.5:c.212C>G
Protein change:
P32R
Links:
dbSNP: rs878854065
NCBI 1000 Genomes Browser:
rs878854065
Molecular consequence:
  • NM_000546.6:c.212C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.212C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.212C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.212C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.95C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.95C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.95C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.95C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.95C>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000285177Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 13, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The corepressor mSin3a interacts with the proline-rich domain of p53 and protects p53 from proteasome-mediated degradation.

Zilfou JT, Hoffman WH, Sank M, George DL, Murphy M.

Mol Cell Biol. 2001 Jun;21(12):3974-85.

PubMed [citation]
PMID:
11359905
PMCID:
PMC87060

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000285177.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, this is a novel missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change impairs binding of TP53 to its co-repressor Sin3, which may reduce TP53 protein stability (PMID: 11359905).  Studies are conflicting regarding the effect of this variant on TP53 transactivation: one study indicates that it has no effect, while another suggests that it partially reduces TP53 function (PMID: 11359905, 12826609). The clinical significance of these findings is unknown. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 237943). This sequence change replaces proline with arginine at codon 71 of the TP53 protein (p.Pro71Arg). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and arginine.

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

Last Updated: Nov 10, 2024