NM_000546.6(TP53):c.361T>C (p.Ser121Pro) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 22, 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:: RCV001059510.8

Allele description [Variation Report for NM_000546.6(TP53):c.361T>C (p.Ser121Pro)]

NM_000546.6(TP53):c.361T>C (p.Ser121Pro)

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.361T>C (p.Ser121Pro)

HGVS:

NC_000017.11:g.7676008A>G
NG_017013.2:g.16543T>C
NM_000546.6:c.361T>CMANE SELECT
NM_001126112.3:c.361T>C
NM_001126113.3:c.361T>C
NM_001126114.3:c.361T>C
NM_001126118.2:c.244T>C
NM_001276695.3:c.244T>C
NM_001276696.3:c.244T>C
NM_001276760.3:c.244T>C
NM_001276761.3:c.244T>C
NP_000537.3:p.Ser121Pro
NP_001119584.1:p.Ser121Pro
NP_001119585.1:p.Ser121Pro
NP_001119586.1:p.Ser121Pro
NP_001119590.1:p.Ser82Pro
NP_001263624.1:p.Ser82Pro
NP_001263625.1:p.Ser82Pro
NP_001263689.1:p.Ser82Pro
NP_001263690.1:p.Ser82Pro
LRG_321t1:c.361T>C
LRG_321:g.16543T>C
NC_000017.10:g.7579326A>G
NM_000546.4:c.361T>C
NM_000546.5:c.361T>C

Protein change:

S121P

Links:

dbSNP: rs2073450567

NCBI 1000 Genomes Browser:

rs2073450567

Molecular consequence:

NM_000546.6:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.244T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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
SCV001224135	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 22, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001224135

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 22, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224135.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces serine with proline at codon 121 of the TP53 protein (p.Ser121Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant has not been reported in the literature in individuals with TP53-related conditions. An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency).

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine