NM_000546.6(TP53):c.658T>C (p.Tyr220His) AND Li-Fraumeni syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 15, 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:: RCV004022253.1

Allele description [Variation Report for NM_000546.6(TP53):c.658T>C (p.Tyr220His)]

NM_000546.6(TP53):c.658T>C (p.Tyr220His)

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.658T>C (p.Tyr220His)

HGVS:

NC_000017.11:g.7674873A>G
NG_017013.2:g.17678T>C
NM_000546.6:c.658T>CMANE SELECT
NM_001126112.3:c.658T>C
NM_001126113.3:c.658T>C
NM_001126114.3:c.658T>C
NM_001126115.2:c.262T>C
NM_001126116.2:c.262T>C
NM_001126117.2:c.262T>C
NM_001126118.2:c.541T>C
NM_001276695.3:c.541T>C
NM_001276696.3:c.541T>C
NM_001276697.3:c.181T>C
NM_001276698.3:c.181T>C
NM_001276699.3:c.181T>C
NM_001276760.3:c.541T>C
NM_001276761.3:c.541T>C
NP_000537.3:p.Tyr220His
NP_000537.3:p.Tyr220His
NP_001119584.1:p.Tyr220His
NP_001119585.1:p.Tyr220His
NP_001119586.1:p.Tyr220His
NP_001119587.1:p.Tyr88His
NP_001119588.1:p.Tyr88His
NP_001119589.1:p.Tyr88His
NP_001119590.1:p.Tyr181His
NP_001263624.1:p.Tyr181His
NP_001263625.1:p.Tyr181His
NP_001263626.1:p.Tyr61His
NP_001263627.1:p.Tyr61His
NP_001263628.1:p.Tyr61His
NP_001263689.1:p.Tyr181His
NP_001263690.1:p.Tyr181His
LRG_321t1:c.658T>C
LRG_321:g.17678T>C
LRG_321p1:p.Tyr220His
NC_000017.10:g.7578191A>G
NM_000546.4:c.658T>C
NM_000546.5:c.658T>C

Protein change:

Y181H

Links:

dbSNP: rs530941076

NCBI 1000 Genomes Browser:

rs530941076

Molecular consequence:

NM_000546.6:c.658T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.658T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.658T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.658T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.262T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.262T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.262T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.181T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.181T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.181T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.541T>C - 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
SCV004932232	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 15, 2024)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7718482, 29979965 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004932232

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Feb 15, 2024)

unknown

clinical testing

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Response of heat shock element within the human HSP70 promoter to mutated p53 genes.

Tsutsumi-Ishii Y, Tadokoro K, Hanaoka F, Tsuchida N.

Cell Growth Differ. 1995 Jan;6(1):1-8.

PubMed [citation]

PMID:: 7718482

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

Details of each submission

From Myriad Genetics, Inc., SCV004932232.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7718482, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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