NM_003722.5(TP63):c.1007G>A (p.Gly336Asp) AND TP63-Related Spectrum Disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 8, 2020
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:: RCV001382756.5

Allele description [Variation Report for NM_003722.5(TP63):c.1007G>A (p.Gly336Asp)]

NM_003722.5(TP63):c.1007G>A (p.Gly336Asp)

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.1007G>A (p.Gly336Asp)

HGVS:

NC_000003.12:g.189868594G>A
NG_007550.3:g.276849G>A
NM_001114978.2:c.1007G>A
NM_001114979.2:c.1007G>A
NM_001114980.2:c.725G>A
NM_001114981.2:c.725G>A
NM_001114982.2:c.725G>A
NM_001329144.2:c.1007G>A
NM_001329145.2:c.725G>A
NM_001329146.2:c.470G>A
NM_001329148.2:c.1007G>A
NM_001329149.2:c.725G>A
NM_001329150.2:c.470G>A
NM_001329964.2:c.1001G>A
NM_003722.5:c.1007G>AMANE SELECT
NP_001108450.1:p.Gly336Asp
NP_001108451.1:p.Gly336Asp
NP_001108452.1:p.Gly242Asp
NP_001108453.1:p.Gly242Asp
NP_001108454.1:p.Gly242Asp
NP_001316073.1:p.Gly336Asp
NP_001316074.1:p.Gly242Asp
NP_001316075.1:p.Gly157Asp
NP_001316077.1:p.Gly336Asp
NP_001316078.1:p.Gly242Asp
NP_001316079.1:p.Gly157Asp
NP_001316893.1:p.Gly334Asp
NP_003713.3:p.Gly336Asp
LRG_428t1:c.1007G>A
LRG_428:g.276849G>A
LRG_428p1:p.Gly336Asp
NC_000003.11:g.189586383G>A

Protein change:

G157D

Links:

dbSNP: rs2108806204

NCBI 1000 Genomes Browser:

rs2108806204

Molecular consequence:

NM_001114978.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114979.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114980.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114981.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114982.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329144.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329145.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329146.2:c.470G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329148.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329149.2:c.725G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329150.2:c.470G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329964.2:c.1001G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003722.5:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 8, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 8, 2020)

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581660.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with ectodermal dysplasia (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 336 of the TP63 protein (p.Gly336Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine