NM_000546.6(TP53):c.59C>T (p.Ser20Leu) 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:: RCV001024777.5

Allele description [Variation Report for NM_000546.6(TP53):c.59C>T (p.Ser20Leu)]

NM_000546.6(TP53):c.59C>T (p.Ser20Leu)

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.59C>T (p.Ser20Leu)

HGVS:

NC_000017.11:g.7676536G>A
NG_017013.2:g.16015C>T
NM_000546.6:c.59C>TMANE SELECT
NM_001126112.3:c.59C>T
NM_001126113.3:c.59C>T
NM_001126114.3:c.59C>T
NM_001126118.2:c.-176C>T
NM_001276695.3:c.-59C>T
NM_001276696.3:c.-59C>T
NM_001276760.3:c.-59C>T
NM_001276761.3:c.-59C>T
NP_000537.3:p.Ser20Leu
NP_001119584.1:p.Ser20Leu
NP_001119585.1:p.Ser20Leu
NP_001119586.1:p.Ser20Leu
LRG_321:g.16015C>T
NC_000017.10:g.7579854G>A
NM_000546.4:c.59C>T

Protein change:

S20L

Links:

dbSNP: rs1597376439

NCBI 1000 Genomes Browser:

rs1597376439

Molecular consequence:

NM_001126118.2:c.-176C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-59C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-59C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-59C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-59C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.59C>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001186856	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 17, 2018)	germline	clinical testing	Citation Link,
SCV002582175	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

SCV001186856

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 17, 2018)

germline

clinical testing

Citation Link,

SCV002582175

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, SCV001186856.4

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

Description

The p.S20L variant (also known as c.59C>T), located in coding exon 1 of the TP53 gene, results from a C to T substitution at nucleotide position 59. The serine at codon 20 is replaced by leucine, an amino acid with dissimilar properties. Yeast based functional studies show this variant has transactivation capacity similar to wild type (IARC TP53 database; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration 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, SCV002582175.1

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine