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NM_000546.6(TP53):c.368C>T (p.Thr123Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 27, 2022
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:
RCV000572422.3

Allele description [Variation Report for NM_000546.6(TP53):c.368C>T (p.Thr123Ile)]

NM_000546.6(TP53):c.368C>T (p.Thr123Ile)

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.368C>T (p.Thr123Ile)
HGVS:
  • NC_000017.11:g.7676001G>A
  • NG_017013.2:g.16550C>T
  • NM_000546.6:c.368C>TMANE SELECT
  • NM_001126112.3:c.368C>T
  • NM_001126113.3:c.368C>T
  • NM_001126114.3:c.368C>T
  • NM_001126118.2:c.251C>T
  • NM_001276695.3:c.251C>T
  • NM_001276696.3:c.251C>T
  • NM_001276760.3:c.251C>T
  • NM_001276761.3:c.251C>T
  • NP_000537.3:p.Thr123Ile
  • NP_001119584.1:p.Thr123Ile
  • NP_001119585.1:p.Thr123Ile
  • NP_001119586.1:p.Thr123Ile
  • NP_001119590.1:p.Thr84Ile
  • NP_001263624.1:p.Thr84Ile
  • NP_001263625.1:p.Thr84Ile
  • NP_001263689.1:p.Thr84Ile
  • NP_001263690.1:p.Thr84Ile
  • LRG_321:g.16550C>T
  • NC_000017.10:g.7579319G>A
  • NM_000546.4:c.368C>T
Protein change:
T123I
Links:
dbSNP: rs1555526486
NCBI 1000 Genomes Browser:
rs1555526486
Molecular consequence:
  • NM_000546.6:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.251C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000664398Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Apr 27, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

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 Ambry Genetics, SCV000664398.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.T123I variant (also known as c.368C>T), located in coding exon 3 of the TP53 gene, results from a C to T substitution at nucleotide position 368. The threonine at codon 123 is replaced by isoleucine, an amino acid with similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have parital loss of transactivation capacity and predicted to affect several p53 isoforms (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant-negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024