NM_000546.6(TP53):c.664C>T (p.Pro222Ser) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 6, 2024
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:: RCV000477098.10

Allele description [Variation Report for NM_000546.6(TP53):c.664C>T (p.Pro222Ser)]

NM_000546.6(TP53):c.664C>T (p.Pro222Ser)

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.664C>T (p.Pro222Ser)

HGVS:

NC_000017.11:g.7674867G>A
NG_017013.2:g.17684C>T
NM_000546.6:c.664C>TMANE SELECT
NM_001126112.3:c.664C>T
NM_001126113.3:c.664C>T
NM_001126114.3:c.664C>T
NM_001126115.2:c.268C>T
NM_001126116.2:c.268C>T
NM_001126117.2:c.268C>T
NM_001126118.2:c.547C>T
NM_001276695.3:c.547C>T
NM_001276696.3:c.547C>T
NM_001276697.3:c.187C>T
NM_001276698.3:c.187C>T
NM_001276699.3:c.187C>T
NM_001276760.3:c.547C>T
NM_001276761.3:c.547C>T
NP_000537.3:p.Pro222Ser
NP_000537.3:p.Pro222Ser
NP_001119584.1:p.Pro222Ser
NP_001119585.1:p.Pro222Ser
NP_001119586.1:p.Pro222Ser
NP_001119587.1:p.Pro90Ser
NP_001119588.1:p.Pro90Ser
NP_001119589.1:p.Pro90Ser
NP_001119590.1:p.Pro183Ser
NP_001263624.1:p.Pro183Ser
NP_001263625.1:p.Pro183Ser
NP_001263626.1:p.Pro63Ser
NP_001263627.1:p.Pro63Ser
NP_001263628.1:p.Pro63Ser
NP_001263689.1:p.Pro183Ser
NP_001263690.1:p.Pro183Ser
LRG_321t1:c.664C>T
LRG_321:g.17684C>T
LRG_321p1:p.Pro222Ser
NC_000017.10:g.7578185G>A
NM_000546.4:c.664C>T
NM_000546.5:c.664C>T

Protein change:

P183S

Links:

dbSNP: rs1060501203

NCBI 1000 Genomes Browser:

rs1060501203

Molecular consequence:

NM_000546.6:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.547C>T - 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
SCV000545333	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 6, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24549055, 29979965, 30224644, 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545333

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 6, 2024)

germline

clinical testing

PubMed (5)
[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

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.

Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, Brault B, Fouillet R, Goardon N, Letac O, Baert-Desurmont S, Tinat J, Bera O, Dugast C, Berthet P, Polycarpe F, Layet V, Hardouin A, Frébourg T, Vaur D.

Eur J Hum Genet. 2014 Nov;22(11):1305-13. doi: 10.1038/ejhg.2014.16. Epub 2014 Feb 19.

PubMed [citation]

PMID:: 24549055
PMCID:: PMC4200427

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000545333.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 222 of the TP53 protein (p.Pro222Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 24549055). ClinVar contains an entry for this variant (Variation ID: 406592). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect 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.

#	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: May 1, 2024

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