NM_000546.6(TP53):c.404G>A (p.Cys135Tyr) AND Li-Fraumeni syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 13, 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:: RCV004019738.1

Allele description [Variation Report for NM_000546.6(TP53):c.404G>A (p.Cys135Tyr)]

NM_000546.6(TP53):c.404G>A (p.Cys135Tyr)

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.404G>A (p.Cys135Tyr)

HGVS:

NC_000017.11:g.7675208C>T
NG_017013.2:g.17343G>A
NM_000546.6:c.404G>AMANE SELECT
NM_001126112.3:c.404G>A
NM_001126113.3:c.404G>A
NM_001126114.3:c.404G>A
NM_001126115.2:c.8G>A
NM_001126116.2:c.8G>A
NM_001126117.2:c.8G>A
NM_001126118.2:c.287G>A
NM_001276695.3:c.287G>A
NM_001276696.3:c.287G>A
NM_001276697.3:c.-74G>A
NM_001276698.3:c.-74G>A
NM_001276699.3:c.-74G>A
NM_001276760.3:c.287G>A
NM_001276761.3:c.287G>A
NP_000537.3:p.Cys135Tyr
NP_000537.3:p.Cys135Tyr
NP_001119584.1:p.Cys135Tyr
NP_001119585.1:p.Cys135Tyr
NP_001119586.1:p.Cys135Tyr
NP_001119587.1:p.Cys3Tyr
NP_001119588.1:p.Cys3Tyr
NP_001119589.1:p.Cys3Tyr
NP_001119590.1:p.Cys96Tyr
NP_001263624.1:p.Cys96Tyr
NP_001263625.1:p.Cys96Tyr
NP_001263689.1:p.Cys96Tyr
NP_001263690.1:p.Cys96Tyr
LRG_321t1:c.404G>A
LRG_321:g.17343G>A
LRG_321p1:p.Cys135Tyr
NC_000017.10:g.7578526C>T
NM_000546.4:c.404G>A
NM_000546.5:c.404G>A
P04637:p.Cys135Tyr
p.C135Y

Protein change:

C135Y

Links:

UniProtKB: P04637#VAR_044756; dbSNP: rs587781991

Molecular consequence:

NM_001276697.3:c.-74G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-74G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-74G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.8G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.8G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.8G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.287G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.287G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.287G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.287G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.287G>A - 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
SCV004933960	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 13, 2024)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7651740, 16247456, 29979965 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004933960

Myriad Genetics, Inc.

criteria provided, single submitter

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

Likely pathogenic
(Feb 13, 2024)

unknown

clinical testing

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Specific DNA binding by different classes of human p53 mutants.

Rolley N, Butcher S, Milner J.

Oncogene. 1995 Aug 17;11(4):763-70.

PubMed [citation]

PMID:: 7651740

Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells.

Ichwan SJ, Yamada S, Sumrejkanchanakij P, Ibrahim-Auerkari E, Eto K, Ikeda MA.

Oncogene. 2006 Feb 23;25(8):1216-24.

PubMed [citation]

PMID:: 16247456

See all PubMed Citations (3)

Details of each submission

From Myriad Genetics, Inc., SCV004933960.1

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

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7651740, 16247456, 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: Jul 27, 2026

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