NM_003722.5(TP63):c.727C>T (p.Arg243Trp) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Apr 1, 2023
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:: RCV000394306.32

Allele description [Variation Report for NM_003722.5(TP63):c.727C>T (p.Arg243Trp)]

NM_003722.5(TP63):c.727C>T (p.Arg243Trp)

Gene:

TP63:tumor protein p63 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q28

Genomic location:

Preferred name:

NM_003722.5(TP63):c.727C>T (p.Arg243Trp)

Other names:

R204W

HGVS:

NC_000003.12:g.189864379C>T
NG_007550.3:g.272634C>T
NM_001114978.2:c.727C>T
NM_001114979.2:c.727C>T
NM_001114980.2:c.445C>T
NM_001114981.2:c.445C>T
NM_001114982.2:c.445C>T
NM_001329144.2:c.727C>T
NM_001329145.2:c.445C>T
NM_001329146.2:c.190C>T
NM_001329148.2:c.727C>T
NM_001329149.2:c.445C>T
NM_001329150.2:c.190C>T
NM_001329964.2:c.721C>T
NM_003722.5:c.727C>TMANE SELECT
NP_001108450.1:p.Arg243Trp
NP_001108451.1:p.Arg243Trp
NP_001108452.1:p.Arg149Trp
NP_001108453.1:p.Arg149Trp
NP_001108454.1:p.Arg149Trp
NP_001316073.1:p.Arg243Trp
NP_001316074.1:p.Arg149Trp
NP_001316075.1:p.Arg64Trp
NP_001316077.1:p.Arg243Trp
NP_001316078.1:p.Arg149Trp
NP_001316079.1:p.Arg64Trp
NP_001316893.1:p.Arg241Trp
NP_003713.3:p.Arg243Trp
LRG_428t1:c.727C>T
LRG_428:g.272634C>T
LRG_428p1:p.Arg243Trp
NC_000003.11:g.189582168C>T
NM_003722.4:c.727C>T
Q9H3D4:p.Arg243Trp

Protein change:

R149W; ARG204TRP

Links:

UniProtKB: Q9H3D4#VAR_020871; OMIM: 603273.0001; dbSNP: rs121908835

NCBI 1000 Genomes Browser:

rs121908835

Molecular consequence:

NM_001114978.2:c.727C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114979.2:c.727C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114980.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114981.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114982.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329144.2:c.727C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329145.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329146.2:c.190C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329148.2:c.727C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329149.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329150.2:c.190C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329964.2:c.721C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003722.5:c.727C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329554	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 13, 2022)	germline	clinical testing	Citation Link,
SCV000708583	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (May 23, 2017)	germline	clinical testing	Citation Link,
SCV001744922	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001746791	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2023)	germline	clinical testing	Citation Link,
SCV001957172	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	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

Details of each submission

From GeneDx, SCV000329554.8

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

Description

Published functional studies demonstrate variant causes a complete loss of transactivation function, and prevents transcription of Hdm2, p21, Shh, and VDR proteins (Khokhar et al., 2008; Kirschner et al. 2010; Monti et al. 2013); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10535733, 31502745, 29620206, 29802835, 29339502, 18626511, 21652629, 20543567, 18792980, 23355676, 23463580, 21078104, 22607287, 32476291, 30088137, 32881366, 28293528, 31333354, 34246755, 17224651, Savukyne_2022)

#	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), SCV000708583.2

#	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 Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001744922.3

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

From CeGaT Center for Human Genetics Tuebingen, SCV001746791.20

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

Description

TP63: PS2, PM2, PM5, PS4:Moderate, PP3, PP4, PS3:Supporting

#	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		2	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001957172.1

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

Last Updated: Oct 20, 2024

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