NM_000546.6(TP53):c.1024C>T (p.Arg342Ter) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Feb 2, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000213069.20

Allele description [Variation Report for NM_000546.6(TP53):c.1024C>T (p.Arg342Ter)]

NM_000546.6(TP53):c.1024C>T (p.Arg342Ter)

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.1024C>T (p.Arg342Ter)

Other names:

p.R342*:CGA>TGA

HGVS:

NC_000017.11:g.7670685G>A
NG_017013.2:g.21866C>T
NM_000546.6:c.1024C>TMANE SELECT
NM_001126112.3:c.1024C>T
NM_001126113.3:c.*43C>T
NM_001126114.3:c.*131C>T
NM_001126115.2:c.628C>T
NM_001126116.2:c.*131C>T
NM_001126117.2:c.*43C>T
NM_001126118.2:c.907C>T
NM_001276695.3:c.*43C>T
NM_001276696.3:c.*131C>T
NM_001276697.3:c.547C>T
NM_001276698.3:c.*131C>T
NM_001276699.3:c.*43C>T
NM_001276760.3:c.907C>T
NM_001276761.3:c.907C>T
NP_000537.3:p.Arg342Ter
NP_000537.3:p.Arg342Ter
NP_001119584.1:p.Arg342Ter
NP_001119587.1:p.Arg210Ter
NP_001119587.1:p.Arg210Ter
NP_001119590.1:p.Arg303Ter
NP_001263626.1:p.Arg183Ter
NP_001263689.1:p.Arg303Ter
NP_001263690.1:p.Arg303Ter
LRG_321t1:c.1024C>T
LRG_321t5:c.628C>T
LRG_321t7:c.*43C>T
LRG_321:g.21866C>T
LRG_321p1:p.Arg342Ter
LRG_321p5:p.Arg210Ter
NC_000017.10:g.7574003G>A
NM_000546.4:c.1024C>T
NM_000546.5:c.1024C>T
NM_001126115.1:c.628C>T
NM_001126117.1:c.*43C>T
p.Arg210*
p.Arg342X
p.R342*

Protein change:

R183*

Links:

dbSNP: rs730882029

NCBI 1000 Genomes Browser:

rs730882029

Molecular consequence:

NM_001126113.3:c.*43C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126114.3:c.*131C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126116.2:c.*131C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126117.2:c.*43C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276695.3:c.*43C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276696.3:c.*131C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276698.3:c.*131C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276699.3:c.*43C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000546.6:c.1024C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.1024C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.628C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.547C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000211808	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 24, 2022)	germline	clinical testing	Citation Link,
SCV000702082	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 6, 2016)	germline	clinical testing	Citation Link,
SCV000884714	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Apr 18, 2018)	germline	clinical testing	Citation Link,
SCV004026013	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 31, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005198833	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000211808.15

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19714490, 28693246, 34249677, 35016432, 24382691, 26425688, 21761402, 20436704, 10519380, 12779080, 18555592, 9115587, 21190917, 16969106, 12509970, 21665182, 28408749, 23484829, 17567834, 28526081, 18511570, 19556618, 26911350, 19711436, 30720243, 31081129, 31105275, 31447099, 32817165, 31742824, 33294277)

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

From Eurofins Ntd Llc (ga), SCV000702082.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	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		1	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884714.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The TP53 c.1024C>T; p.Arg342Ter variant (rs730882029) is reported in the germline of at least two individuals with suspected Li Fraumeni syndrome (Hettmer 2014, Trkova 2007). The variant is listed as pathogenic by several sources in the ClinVar database (Variation ID: 182970), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is classified as pathogenic. References: Hettmer S et al. Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers. Cancer. 2014 Apr 1;120(7):1068-75. Trkova M et al. Telomere length in peripheral blood cells of germline TP53 mutation carriers is shorter than that of normal individuals of corresponding age. Cancer. 2007 Aug 1;110(3):694-702.

#	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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV004026013.1

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

Description

PVS1, PM1, PM2_SUP

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

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198833.1

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

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

Last Updated: Jan 13, 2025

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