NM_003722.5(TP63):c.728G>A (p.Arg243Gln) AND TP63-Related Spectrum Disorders

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 10, 2023
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:: RCV000705452.6

Allele description

NM_003722.5(TP63):c.728G>A (p.Arg243Gln)

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.728G>A (p.Arg243Gln)

Other names:

R204Q

HGVS:

NC_000003.12:g.189864380G>A
NG_007550.3:g.272635G>A
NM_001114978.2:c.728G>A
NM_001114979.2:c.728G>A
NM_001114980.2:c.446G>A
NM_001114981.2:c.446G>A
NM_001114982.2:c.446G>A
NM_001329144.2:c.728G>A
NM_001329145.2:c.446G>A
NM_001329146.2:c.191G>A
NM_001329148.2:c.728G>A
NM_001329149.2:c.446G>A
NM_001329150.2:c.191G>A
NM_001329964.2:c.722G>A
NM_003722.5:c.728G>AMANE SELECT
NP_001108450.1:p.Arg243Gln
NP_001108451.1:p.Arg243Gln
NP_001108452.1:p.Arg149Gln
NP_001108453.1:p.Arg149Gln
NP_001108454.1:p.Arg149Gln
NP_001316073.1:p.Arg243Gln
NP_001316074.1:p.Arg149Gln
NP_001316075.1:p.Arg64Gln
NP_001316077.1:p.Arg243Gln
NP_001316078.1:p.Arg149Gln
NP_001316079.1:p.Arg64Gln
NP_001316893.1:p.Arg241Gln
NP_003713.3:p.Arg243Gln
LRG_428t1:c.728G>A
LRG_428:g.272635G>A
LRG_428p1:p.Arg243Gln
NC_000003.11:g.189582169G>A
NM_003722.4:c.728G>A
Q9H3D4:p.Arg243Gln

Protein change:

R149Q; ARG204GLN

Links:

UniProtKB: Q9H3D4#VAR_020870; OMIM: 603273.0002; dbSNP: rs121908836

NCBI 1000 Genomes Browser:

rs121908836

Molecular consequence:

NM_001114978.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114979.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114980.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114981.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114982.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329144.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329145.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329146.2:c.191G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329148.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329149.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329150.2:c.191G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329964.2:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003722.5:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: TP63-Related Spectrum Disorders
Identifiers:: MedGen: CN239305

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MBD1 methyl-CpG binding domain protein 1 [Homo sapiens]
MBD1 methyl-CpG binding domain protein 1 [Homo sapiens]
Gene ID:4152

Gene
Gene Links for GEO Profiles (Select 132378608) (1)
Gene
Fuligo intermedia elongation factor 1-alpha (EF1-alpha) gene, partial sequence
Fuligo intermedia elongation factor 1-alpha (EF1-alpha) gene, partial sequence
gi|323148805|gb|GU563914.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000834450	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 10, 2023)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 12525544, 18626511, 18792980, 20543567, 21078104, 21652629, 23355676, 23463580, 10535733, 28293528, 29620206, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834450

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 10, 2023)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

P63 mutations are not a major cause of non-syndromic split hand/foot malformation.

de Mollerat XJ, Everman DB, Morgan CT, Clarkson KB, Rogers RC, Colby RS, Aylsworth AS, Graham JM Jr, Stevenson RE, Schwartz CE.

J Med Genet. 2003 Jan;40(1):55-61. No abstract available.

PubMed [citation]

PMID:: 12525544
PMCID:: PMC1735259

Differential effects of p63 mutants on transactivation of p53 and/or p63 responsive genes.

Khokhar SK, Kommagani R, Kadakia MP.

Cell Res. 2008 Oct;18(10):1061-73. doi: 10.1038/cr.2008.82.

PubMed [citation]

PMID:: 18626511
PMCID:: PMC2760224

See all PubMed Citations (12)

Details of each submission

From Invitae, SCV000834450.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg243 amino acid residue in TP63. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10535733, 12525544, 18626511, 18792980, 20543567, 21078104, 21652629, 23355676, 23463580). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP63 protein function. ClinVar contains an entry for this variant (Variation ID: 6528). This variant is also known as p.Arg204Gln. This missense change has been observed in individual(s) with autosomal dominant split-hand-split-foot malformation or SHFM and ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome (PMID: 10535733, 28293528, 29620206). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 243 of the TP63 protein (p.Arg243Gln).

#	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: Feb 20, 2024

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