NM_000546.6(TP53):c.718A>C (p.Ser240Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 11, 2019
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:: RCV001026129.3

Allele description [Variation Report for NM_000546.6(TP53):c.718A>C (p.Ser240Arg)]

NM_000546.6(TP53):c.718A>C (p.Ser240Arg)

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.718A>C (p.Ser240Arg)

HGVS:

NC_000017.11:g.7674245T>G
NG_017013.2:g.18306A>C
NM_000546.6:c.718A>CMANE SELECT
NM_001126112.3:c.718A>C
NM_001126113.3:c.718A>C
NM_001126114.3:c.718A>C
NM_001126115.2:c.322A>C
NM_001126116.2:c.322A>C
NM_001126117.2:c.322A>C
NM_001126118.2:c.601A>C
NM_001276695.3:c.601A>C
NM_001276696.3:c.601A>C
NM_001276697.3:c.241A>C
NM_001276698.3:c.241A>C
NM_001276699.3:c.241A>C
NM_001276760.3:c.601A>C
NM_001276761.3:c.601A>C
NP_000537.3:p.Ser240Arg
NP_001119584.1:p.Ser240Arg
NP_001119585.1:p.Ser240Arg
NP_001119586.1:p.Ser240Arg
NP_001119587.1:p.Ser108Arg
NP_001119588.1:p.Ser108Arg
NP_001119589.1:p.Ser108Arg
NP_001119590.1:p.Ser201Arg
NP_001263624.1:p.Ser201Arg
NP_001263625.1:p.Ser201Arg
NP_001263626.1:p.Ser81Arg
NP_001263627.1:p.Ser81Arg
NP_001263628.1:p.Ser81Arg
NP_001263689.1:p.Ser201Arg
NP_001263690.1:p.Ser201Arg
LRG_321:g.18306A>C
NC_000017.10:g.7577563T>G
NM_000546.4:c.718A>C

Protein change:

S108R

Links:

dbSNP: rs1567549584

NCBI 1000 Genomes Browser:

rs1567549584

Molecular consequence:

NM_000546.6:c.718A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.718A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.718A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.718A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.322A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.322A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.322A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.601A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.601A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.601A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.241A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.241A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.241A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.601A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.601A>C - 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
SCV001188450	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Dec 11, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001188450

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Dec 11, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV001188450.4

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

Description

The p.S240R variant (also known as c.718A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide position 718. The serine at codon 240 is replaced by arginine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partial loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration 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). Though this exact alteration has not been published in the literature, another alteration at this same codon (p.S240G/c.718A>G) has been reported in an individual with Li-Fraumeni syndrome (Villani A et al. Lancet Oncol. 2016 Sep;17(9):1295-305). This amino acid position is highly 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.

#	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

Last Updated: Sep 29, 2024

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