NM_000546.6(TP53):c.902C>T (p.Pro301Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000574619.5

Allele description [Variation Report for NM_000546.6(TP53):c.902C>T (p.Pro301Leu)]

NM_000546.6(TP53):c.902C>T (p.Pro301Leu)

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.902C>T (p.Pro301Leu)

HGVS:

NC_000017.11:g.7673718G>A
NG_017013.2:g.18833C>T
NM_000546.6:c.902C>TMANE SELECT
NM_001126112.3:c.902C>T
NM_001126113.3:c.902C>T
NM_001126114.3:c.902C>T
NM_001126115.2:c.506C>T
NM_001126116.2:c.506C>T
NM_001126117.2:c.506C>T
NM_001126118.2:c.785C>T
NM_001276695.3:c.785C>T
NM_001276696.3:c.785C>T
NM_001276697.3:c.425C>T
NM_001276698.3:c.425C>T
NM_001276699.3:c.425C>T
NM_001276760.3:c.785C>T
NM_001276761.3:c.785C>T
NP_000537.3:p.Pro301Leu
NP_001119584.1:p.Pro301Leu
NP_001119585.1:p.Pro301Leu
NP_001119586.1:p.Pro301Leu
NP_001119587.1:p.Pro169Leu
NP_001119588.1:p.Pro169Leu
NP_001119589.1:p.Pro169Leu
NP_001119590.1:p.Pro262Leu
NP_001263624.1:p.Pro262Leu
NP_001263625.1:p.Pro262Leu
NP_001263626.1:p.Pro142Leu
NP_001263627.1:p.Pro142Leu
NP_001263628.1:p.Pro142Leu
NP_001263689.1:p.Pro262Leu
NP_001263690.1:p.Pro262Leu
LRG_321:g.18833C>T
NC_000017.10:g.7577036G>A
NM_000546.4:c.902C>T

Protein change:

P142L

Links:

dbSNP: rs1555525067

NCBI 1000 Genomes Browser:

rs1555525067

Molecular consequence:

NM_000546.6:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.506C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.506C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.506C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.425C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.425C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.425C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.785C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000665160	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 1, 2016)	germline	clinical testing	Citation Link,
SCV002581983	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000665160

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 1, 2016)

germline

clinical testing

Citation Link,

SCV002581983

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000665160.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.P301L variant (also known as c.902C>T), located in coding exon 7 of the TP53 gene, results from a C to T substitution at nucleotide position 902. The proline at codon 301 is replaced by leucine, an amino acid with similar properties. This alteration has been reported as a somatic mutation 5 times in various tumors, but not as a germline mutation by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum Mutat. 2007 Jun; 28(6):622-9). Yeast based functional studies have demonstrated this alteration has transactvation capacity similar to wild type protein (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul; 100(14):8424-9). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0005% (greater than 200000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

#	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

From Genome-Nilou Lab, SCV002581983.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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