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NM_000546.6(TP53):c.814G>A (p.Val272Met) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 10, 2024
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:
RCV000165304.9

Allele description [Variation Report for NM_000546.6(TP53):c.814G>A (p.Val272Met)]

NM_000546.6(TP53):c.814G>A (p.Val272Met)

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.814G>A (p.Val272Met)
HGVS:
  • NC_000017.11:g.7673806C>T
  • NG_017013.2:g.18745G>A
  • NM_000546.6:c.814G>AMANE SELECT
  • NM_001126112.3:c.814G>A
  • NM_001126113.3:c.814G>A
  • NM_001126114.3:c.814G>A
  • NM_001126115.2:c.418G>A
  • NM_001126116.2:c.418G>A
  • NM_001126117.2:c.418G>A
  • NM_001126118.2:c.697G>A
  • NM_001276695.3:c.697G>A
  • NM_001276696.3:c.697G>A
  • NM_001276697.3:c.337G>A
  • NM_001276698.3:c.337G>A
  • NM_001276699.3:c.337G>A
  • NM_001276760.3:c.697G>A
  • NM_001276761.3:c.697G>A
  • NP_000537.3:p.Val272Met
  • NP_000537.3:p.Val272Met
  • NP_001119584.1:p.Val272Met
  • NP_001119585.1:p.Val272Met
  • NP_001119586.1:p.Val272Met
  • NP_001119587.1:p.Val140Met
  • NP_001119588.1:p.Val140Met
  • NP_001119589.1:p.Val140Met
  • NP_001119590.1:p.Val233Met
  • NP_001263624.1:p.Val233Met
  • NP_001263625.1:p.Val233Met
  • NP_001263626.1:p.Val113Met
  • NP_001263627.1:p.Val113Met
  • NP_001263628.1:p.Val113Met
  • NP_001263689.1:p.Val233Met
  • NP_001263690.1:p.Val233Met
  • LRG_321t1:c.814G>A
  • LRG_321t3:c.814G>A
  • LRG_321:g.18745G>A
  • LRG_321p1:p.Val272Met
  • NC_000017.10:g.7577124C>T
  • NM_000546.4:c.814G>A
  • NM_000546.5(TP53):c.814G>A
  • NM_000546.5:c.814G>A
  • P04637:p.Val272Met
  • p.V272M
Protein change:
V113M
Links:
UniProtKB: P04637#VAR_045354; dbSNP: rs121912657
NCBI 1000 Genomes Browser:
rs121912657
Molecular consequence:
  • NM_000546.6:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.418G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.418G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.418G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.697G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000216025Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 10, 2024) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Evaluation of TP53 mutations with the AmpliChip p53 research test in chronic lymphocytic leukemia: correlation with clinical outcome and gene expression profiling.

Chiaretti S, Tavolaro S, Marinelli M, Messina M, Del Giudice I, Mauro FR, Santangelo S, Piciocchi A, Peragine N, Truong S, Patten N, Ghia EM, Torrente I, De Propris MS, Nanni M, Lawrence J, Guarini A, Foà R.

Genes Chromosomes Cancer. 2011 Apr;50(4):263-74. doi: 10.1002/gcc.20852. Epub 2011 Jan 13.

PubMed [citation]
PMID:
21319261

Identification of molecular and functional patterns of p53 alterations in chronic lymphocytic leukemia patients in different phases of the disease.

Marinelli M, Peragine N, Di Maio V, Chiaretti S, De Propris MS, Raponi S, Tavolaro S, Mauro FR, Del Giudice I, Guarini A, Foà R.

Haematologica. 2013 Mar;98(3):371-5. doi: 10.3324/haematol.2012.069906. Epub 2012 Sep 14.

PubMed [citation]
PMID:
22983585
PMCID:
PMC3659928
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000216025.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.V272M pathogenic mutation (also known as c.814G>A), located in coding exon 7 of the TP53 gene, results from a G to A substitution at nucleotide position 814. The valine at codon 272 is replaced by methionine, an amino acid with highly similar properties. This alteration has been detected in a French family with features suggestive of Li-Fraumeni syndrome, a patient diagnosed with rhabdomyosarcoma at age 1 and osteosarcoma at age 2, as well as a patient diagnosed with medulloblastoma at age 3 (Bougeard G et al. J. Med. Genet. 2008 Aug;45(8):535-8; Renaux-Petel M et al. J. Med. Genet. 2017 Oct 25). This alteration was also identified in a patient with late onset adrenal cortical carcinoma (Raymond VM et al. J. Clin. Endocrinol. Metab. 2013 Jan; 98(1):E119-25). The p.V272M alteration has been reported as a somatic alteration in a variety of tumors (Marinelli M et al. Haematologica 2013 Mar; 98(3):371-5; Chiaretti S et al. Genes Chromosomes Cancer 2011 Apr; 50(4):263-74; Chang MT et al. Cancer Discov. 2018 02;8:174-183). This alteration is a well-known temperature sensitive alteration that causes abnormal protein folding and prevents DNA binding at temperatures above 37 degrees Celsius (da Costa NM et al. Cell Cycle 2012 Dec;11(24):4570-8). Functional studies have demonstrated that this alteration interferes with p53 up-regulation in response to DNA damaging agents and shows loss of transactivation capacity in yeast based assays (Barnas Cet al. Int. J. Cancer 1997 Mar;71(1):79-87). Studies conducted in human cell lines indicate this alteration has a dominant negative effect and is deficient 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. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 20, 2024