NM_001308093.3(GATA4):c.781C>T (p.Arg261Trp) AND Atrioventricular septal defect 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 8, 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:: RCV003642632.2

Allele description [Variation Report for NM_001308093.3(GATA4):c.781C>T (p.Arg261Trp)]

NM_001308093.3(GATA4):c.781C>T (p.Arg261Trp)

Gene:

GATA4:GATA binding protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.1

Genomic location:

Preferred name:

NM_001308093.3(GATA4):c.781C>T (p.Arg261Trp)

HGVS:

NC_000008.11:g.11749080C>T
NG_008177.2:g.77162C>T
NM_001308093.3:c.781C>TMANE SELECT
NM_001308094.2:c.160C>T
NM_001374273.1:c.160C>T
NM_001374274.1:c.160C>T
NM_002052.5:c.778C>T
NP_001295022.1:p.Arg261Trp
NP_001295023.1:p.Arg54Trp
NP_001361202.1:p.Arg54Trp
NP_001361203.1:p.Arg54Trp
NP_002043.2:p.Arg260Trp
NC_000008.10:g.11606589C>T

Protein change:

R260W

Molecular consequence:

NM_001308093.3:c.781C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.160C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.160C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374274.1:c.160C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.778C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrioventricular septal defect 4 (AVSD4)
Identifiers:: MONDO: MONDO:0013747; MedGen: C3280781; OMIM: 614430

Recent activity

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insulin-like growth factor binding protein-1, partial [Danio rerio]
insulin-like growth factor binding protein-1, partial [Danio rerio]
gi|57157669|dbj|BAD83799.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004524788	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29874181, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004524788

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 8, 2023)

germline

clinical testing

PubMed (2)
[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

Whole-Exome Sequencing Reveals GATA4 and PTEN Mutations as a Potential Digenic Cause of Left Ventricular Noncompaction.

Tang VT, Arscott P, Helms AS, Day SM.

Circ Genom Precis Med. 2018 Jan;11(1):e001966. doi: 10.1161/CIRCGEN.117.001966. No abstract available.

PubMed [citation]

PMID:: 29874181

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, SCV004524788.1

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 260 of the GATA4 protein (p.Arg260Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with left ventricular apical noncompaction (PMID: 29874181). 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 GATA4 protein function. Experimental studies have shown that this missense change affects GATA4 function (PMID: 29874181). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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