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NM_000546.6(TP53):c.569C>T (p.Pro190Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 21, 2022
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:
RCV002350050.2

Allele description

NM_000546.6(TP53):c.569C>T (p.Pro190Leu)

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.569C>T (p.Pro190Leu)
HGVS:
  • NC_000017.11:g.7674962G>A
  • NG_017013.2:g.17589C>T
  • NM_000546.6:c.569C>TMANE SELECT
  • NM_001126112.3:c.569C>T
  • NM_001126113.3:c.569C>T
  • NM_001126114.3:c.569C>T
  • NM_001126115.2:c.173C>T
  • NM_001126116.2:c.173C>T
  • NM_001126117.2:c.173C>T
  • NM_001126118.2:c.452C>T
  • NM_001276695.3:c.452C>T
  • NM_001276696.3:c.452C>T
  • NM_001276697.3:c.92C>T
  • NM_001276698.3:c.92C>T
  • NM_001276699.3:c.92C>T
  • NM_001276760.3:c.452C>T
  • NM_001276761.3:c.452C>T
  • NP_000537.3:p.Pro190Leu
  • NP_000537.3:p.Pro190Leu
  • NP_001119584.1:p.Pro190Leu
  • NP_001119585.1:p.Pro190Leu
  • NP_001119586.1:p.Pro190Leu
  • NP_001119587.1:p.Pro58Leu
  • NP_001119588.1:p.Pro58Leu
  • NP_001119589.1:p.Pro58Leu
  • NP_001119590.1:p.Pro151Leu
  • NP_001263624.1:p.Pro151Leu
  • NP_001263625.1:p.Pro151Leu
  • NP_001263626.1:p.Pro31Leu
  • NP_001263627.1:p.Pro31Leu
  • NP_001263628.1:p.Pro31Leu
  • NP_001263689.1:p.Pro151Leu
  • NP_001263690.1:p.Pro151Leu
  • LRG_321t1:c.569C>T
  • LRG_321t2:c.569C>T
  • LRG_321:g.17589C>T
  • LRG_321p1:p.Pro190Leu
  • NC_000017.10:g.7578280G>A
  • NM_000546.4:c.569C>T
  • NM_000546.5:c.569C>T
  • NM_001126112.2(TP53):c.569C>T
  • p.Pro190Leu
Protein change:
P151L
Links:
dbSNP: rs876660825
NCBI 1000 Genomes Browser:
rs876660825
Molecular consequence:
  • NM_000546.6:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.173C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.173C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.173C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.92C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.92C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.92C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV002647488Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Likely pathogenic
(Apr 21, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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.

PubMed [citation]
PMID:
29979965
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002647488.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.P190L variant (also known as c.569C>T), located in coding exon 5 of the TP53 gene, results from a C to T substitution at nucleotide position 569. The proline at codon 190 is replaced by leucine, an amino acid with similar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with TP53-related disease (IARC TP53 database, personal communication). This variant is in the DNA binding domain of the TP53 protein and is reported to have a partial loss of transactivation capacity in two different yeast based assays (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9, Jordan JJ, Mol. Cancer Res. 2010 May; 8(5):701-16). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Feb 28, 2024