NM_000546.6(TP53):c.353C>T (p.Thr118Ile) AND Li-Fraumeni syndrome 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 3, 2021
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV001724024.3

Allele description [Variation Report for NM_000546.6(TP53):c.353C>T (p.Thr118Ile)]

NM_000546.6(TP53):c.353C>T (p.Thr118Ile)

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.353C>T (p.Thr118Ile)

Other names:

NM_000546.5(TP53):c.353C>T; p.Thr118Ile

HGVS:

NC_000017.11:g.7676016G>A
NG_017013.2:g.16535C>T
NM_000546.6:c.353C>TMANE SELECT
NM_001126112.3:c.353C>T
NM_001126113.3:c.353C>T
NM_001126114.3:c.353C>T
NM_001126118.2:c.236C>T
NM_001276695.3:c.236C>T
NM_001276696.3:c.236C>T
NM_001276760.3:c.236C>T
NM_001276761.3:c.236C>T
NP_000537.3:p.Thr118Ile
NP_000537.3:p.Thr118Ile
NP_001119584.1:p.Thr118Ile
NP_001119585.1:p.Thr118Ile
NP_001119586.1:p.Thr118Ile
NP_001119590.1:p.Thr79Ile
NP_001263624.1:p.Thr79Ile
NP_001263625.1:p.Thr79Ile
NP_001263689.1:p.Thr79Ile
NP_001263690.1:p.Thr79Ile
LRG_321t1:c.353C>T
LRG_321:g.16535C>T
LRG_321p1:p.Thr118Ile
NC_000017.10:g.7579334G>A
NM_000546.4:c.353C>T
NM_000546.5:c.353C>T

Protein change:

T118I

Links:

dbSNP: rs1064794141

NCBI 1000 Genomes Browser:

rs1064794141

Molecular consequence:

NM_000546.6:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.236C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001949915	ClinGen TP53 Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen TP53 ACMG Specifications v1.2)	Uncertain significance (Aug 3, 2021)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 12826609, 29979965, 30224644 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001949915

ClinGen TP53 Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1.2)

Uncertain significance
(Aug 3, 2021)

germline

curation

PubMed (3)
[See all records that cite these PMIDs]

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	curation

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

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 (3)

Details of each submission

From ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001949915.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

Description

This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). This variant has been observed in 2 60+ year old females without a cancer diagnosis (BS2_Supporting; Ambry Genetics). Transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). In summary, the clinical significance of TP53 c.353C>T (p.Thr118Ile) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, PP3_Moderate, BS2_Supporting, BS3

#	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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