NM_000546.6(TP53):c.634T>A (p.Phe212Ile) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 2, 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:: RCV000687495.8

Allele description [Variation Report for NM_000546.6(TP53):c.634T>A (p.Phe212Ile)]

NM_000546.6(TP53):c.634T>A (p.Phe212Ile)

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.634T>A (p.Phe212Ile)

HGVS:

NC_000017.11:g.7674897A>T
NG_017013.2:g.17654T>A
NM_000546.6:c.634T>AMANE SELECT
NM_001126112.3:c.634T>A
NM_001126113.3:c.634T>A
NM_001126114.3:c.634T>A
NM_001126115.2:c.238T>A
NM_001126116.2:c.238T>A
NM_001126117.2:c.238T>A
NM_001126118.2:c.517T>A
NM_001276695.3:c.517T>A
NM_001276696.3:c.517T>A
NM_001276697.3:c.157T>A
NM_001276698.3:c.157T>A
NM_001276699.3:c.157T>A
NM_001276760.3:c.517T>A
NM_001276761.3:c.517T>A
NP_000537.3:p.Phe212Ile
NP_000537.3:p.Phe212Ile
NP_001119584.1:p.Phe212Ile
NP_001119585.1:p.Phe212Ile
NP_001119586.1:p.Phe212Ile
NP_001119587.1:p.Phe80Ile
NP_001119588.1:p.Phe80Ile
NP_001119589.1:p.Phe80Ile
NP_001119590.1:p.Phe173Ile
NP_001263624.1:p.Phe173Ile
NP_001263625.1:p.Phe173Ile
NP_001263626.1:p.Phe53Ile
NP_001263627.1:p.Phe53Ile
NP_001263628.1:p.Phe53Ile
NP_001263689.1:p.Phe173Ile
NP_001263690.1:p.Phe173Ile
LRG_321t1:c.634T>A
LRG_321:g.17654T>A
LRG_321p1:p.Phe212Ile
NC_000017.10:g.7578215A>T
NM_000546.4:c.634T>A
NM_000546.5:c.634T>A

Protein change:

F173I

Links:

dbSNP: rs1064795766

NCBI 1000 Genomes Browser:

rs1064795766

Molecular consequence:

NM_000546.6:c.634T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.634T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.634T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.634T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.238T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.238T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.238T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.517T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.517T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.517T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.157T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.157T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.157T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.517T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.517T>A - 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
SCV000815064	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 2, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25584008, 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815064

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 2, 2023)

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

Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study.

Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, Malkin D.

J Clin Oncol. 2015 Feb 20;33(6):602-9. doi: 10.1200/JCO.2013.52.6863. Epub 2015 Jan 12.

PubMed [citation]

PMID:: 25584008
PMCID:: PMC4517369

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000815064.5

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

Description

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. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 25584008). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 422414). This missense change has been observed in individual(s) with clinical features of TP53-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 212 of the TP53 protein (p.Phe212Ile).

#	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: Feb 20, 2024

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