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NM_000546.6(TP53):c.214C>A (p.Pro72Thr) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 21, 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:
RCV001221060.6

Allele description [Variation Report for NM_000546.6(TP53):c.214C>A (p.Pro72Thr)]

NM_000546.6(TP53):c.214C>A (p.Pro72Thr)

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.214C>A (p.Pro72Thr)
HGVS:
  • NC_000017.11:g.7676155G>T
  • NG_017013.2:g.16396C>A
  • NM_000546.6:c.214C>AMANE SELECT
  • NM_001126112.3:c.214C>A
  • NM_001126113.3:c.214C>A
  • NM_001126114.3:c.214C>A
  • NM_001126118.2:c.97C>A
  • NM_001276695.3:c.97C>A
  • NM_001276696.3:c.97C>A
  • NM_001276760.3:c.97C>A
  • NM_001276761.3:c.97C>A
  • NP_000537.3:p.Pro72Thr
  • NP_000537.3:p.Pro72Thr
  • NP_001119584.1:p.Pro72Thr
  • NP_001119585.1:p.Pro72Thr
  • NP_001119586.1:p.Pro72Thr
  • NP_001119590.1:p.Pro33Thr
  • NP_001263624.1:p.Pro33Thr
  • NP_001263625.1:p.Pro33Thr
  • NP_001263689.1:p.Pro33Thr
  • NP_001263690.1:p.Pro33Thr
  • LRG_321t1:c.214C>A
  • LRG_321:g.16396C>A
  • LRG_321p1:p.Pro72Thr
  • NC_000017.10:g.7579473G>T
  • NM_000546.4:c.214C>A
  • NM_000546.5:c.214C>A
Protein change:
P33T
Links:
dbSNP: rs587782769
NCBI 1000 Genomes Browser:
rs587782769
Molecular consequence:
  • NM_000546.6:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.97C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.97C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.97C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.97C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.97C>A - 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
SCV001393083Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 21, 2023) 		germlineclinical testing

PubMed (4)
[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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001393083.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 72 of the TP53 protein (p.Pro72Thr). This variant is present in population databases (rs587782769, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 232750). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. 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.

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

Last Updated: Nov 10, 2024