NM_003722.5(TP63):c.955C>T (p.Arg319Cys) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jul 5, 2022
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:: RCV001280776.9

Allele description [Variation Report for NM_003722.5(TP63):c.955C>T (p.Arg319Cys)]

NM_003722.5(TP63):c.955C>T (p.Arg319Cys)

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.955C>T (p.Arg319Cys)

Other names:

R280C

HGVS:

NC_000003.12:g.189867905C>T
NG_007550.3:g.276160C>T
NM_001114978.2:c.955C>T
NM_001114979.2:c.955C>T
NM_001114980.2:c.673C>T
NM_001114981.2:c.673C>T
NM_001114982.2:c.673C>T
NM_001329144.2:c.955C>T
NM_001329145.2:c.673C>T
NM_001329146.2:c.418C>T
NM_001329148.2:c.955C>T
NM_001329149.2:c.673C>T
NM_001329150.2:c.418C>T
NM_001329964.2:c.949C>T
NM_003722.5:c.955C>TMANE SELECT
NP_001108450.1:p.Arg319Cys
NP_001108451.1:p.Arg319Cys
NP_001108452.1:p.Arg225Cys
NP_001108453.1:p.Arg225Cys
NP_001108454.1:p.Arg225Cys
NP_001316073.1:p.Arg319Cys
NP_001316074.1:p.Arg225Cys
NP_001316075.1:p.Arg140Cys
NP_001316077.1:p.Arg319Cys
NP_001316078.1:p.Arg225Cys
NP_001316079.1:p.Arg140Cys
NP_001316893.1:p.Arg317Cys
NP_003713.3:p.Arg319Cys
LRG_428t1:c.955C>T
LRG_428:g.276160C>T
LRG_428p1:p.Arg319Cys
NC_000003.11:g.189585694C>T
NM_003722.4:c.955C>T
Q9H3D4:p.Arg319Cys

Protein change:

R140C; ARG280CYS

Links:

UniProtKB: Q9H3D4#VAR_020874; OMIM: 603273.0006; dbSNP: rs121908839

NCBI 1000 Genomes Browser:

rs121908839

Molecular consequence:

NM_001114978.2:c.955C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114979.2:c.955C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114980.2:c.673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114981.2:c.673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114982.2:c.673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329144.2:c.955C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329145.2:c.673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329146.2:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329148.2:c.955C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329149.2:c.673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329150.2:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001329964.2:c.949C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003722.5:c.955C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001468099	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001832271	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Nov 14, 2019)	germline	clinical testing	Citation Link,
SCV002015680	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 5, 2022)	germline	clinical testing	Citation Link,
SCV003820391	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 15, 2021)	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	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV001468099.1

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

Description

PS3, PS4, PP1, PP3, PM1, PM2

#	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 Blueprint Genetics, SCV001832271.1

#	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

From GeneDx, SCV002015680.3

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

Description

Identified in multiple individuals with TP63-related disorders referred for genetic testing at GeneDx and in published literature (Ianakiev et al., 2000; Yang et al., 2017); Published functional studies demonstrate interference with TP63 protein function and inhibition of the wild-type protein in a dominant-negative manner (Khokhar et al., 2008; Serra et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22574117, 24460914, 12161593, 22069181, 29620206, 21211247, 15324320, 31050217, 28420484, 18626511, 10839977, 17224651, 21652629)

#	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 Revvity Omics, Revvity, SCV003820391.2

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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