NM_000546.6(TP53):c.373A>C (p.Thr125Pro) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 25, 2023
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:: RCV001041773.9

Allele description [Variation Report for NM_000546.6(TP53):c.373A>C (p.Thr125Pro)]

NM_000546.6(TP53):c.373A>C (p.Thr125Pro)

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.373A>C (p.Thr125Pro)

HGVS:

NC_000017.11:g.7675996T>G
NG_017013.2:g.16555A>C
NM_000546.4:c.373A>C
NM_000546.6:c.373A>CMANE SELECT
NM_001126112.3:c.373A>C
NM_001126113.3:c.373A>C
NM_001126114.3:c.373A>C
NM_001126118.2:c.256A>C
NM_001276695.3:c.256A>C
NM_001276696.3:c.256A>C
NM_001276760.3:c.256A>C
NM_001276761.3:c.256A>C
NP_000537.3:p.Thr125Pro
NP_000537.3:p.Thr125Pro
NP_001119584.1:p.Thr125Pro
NP_001119585.1:p.Thr125Pro
NP_001119586.1:p.Thr125Pro
NP_001119590.1:p.Thr86Pro
NP_001263624.1:p.Thr86Pro
NP_001263625.1:p.Thr86Pro
NP_001263689.1:p.Thr86Pro
NP_001263690.1:p.Thr86Pro
LRG_321t1:c.373A>C
LRG_321:g.16555A>C
LRG_321p1:p.Thr125Pro
NC_000017.10:g.7579314T>G
NM_000546.5:c.373A>C
NM_000546.6:c.373A>C

Protein change:

T125P

Links:

dbSNP: rs1057520003

NCBI 1000 Genomes Browser:

rs1057520003

Molecular consequence:

NM_000546.6:c.373A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.373A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.373A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.373A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.256A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.256A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.256A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.256A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.256A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001205410	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 25, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12826609, 25896519, 29753700, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001205410

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 25, 2023)

germline

clinical testing

PubMed (4)
[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

Germline TP53 variants and susceptibility to osteosarcoma.

Mirabello L, Yeager M, Mai PL, Gastier-Foster JM, Gorlick R, Khanna C, Patiño-Garcia A, Sierrasesúmaga L, Lecanda F, Andrulis IL, Wunder JS, Gokgoz N, Barkauskas DA, Zhang X, Vogt A, Jones K, Boland JF, Chanock SJ, Savage SA.

J Natl Cancer Inst. 2015 Apr 20;107(7). doi:pii: djv101. 10.1093/jnci/djv101. Print 2015 Jul.

PubMed [citation]

PMID:: 25896519
PMCID:: PMC4651039

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205410.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Experimental studies have shown that this missense change affects TP53 function (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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 376666). This missense change has been observed in individual(s) with medulloblastoma and/or osteosarcoma (PMID: 25896519, 29753700; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 125 of the TP53 protein (p.Thr125Pro).

#	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

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