Submissions for variant NM_001308093.3(GATA4):c.1276G>A (p.Asp426Asn)

gnomAD frequency: 0.00003  dbSNP: rs56208331

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000190715	SCV000244156	uncertain significance	Inborn genetic diseases	2013-07-01	criteria provided, single submitter	clinical testing	​Based on the available evidence, the deleterious nature of this alteration is uncertain.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000431077	SCV000511051	benign	not provided	2016-09-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000988036	SCV000652001	benign	Atrioventricular septal defect 4	2023-12-31	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626818	SCV000747521	uncertain significance	Pulmonic stenosis; Tricuspid regurgitation; Pulmonary valve atresia	2017-01-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000988036	SCV001137587	benign	Atrioventricular septal defect 4	2023-08-22	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000009601	SCV001435185	benign	Tetralogy of Fallot		criteria provided, single submitter	research	The heterozygous p.Asp425Asn variant in GATA4 in 2 individuals with congenital heart defects, including an individual with an unaffected parent and the variant (PMID: 18055909), and has been identified in >1% of South Asian chromosomes and 1 homozygote by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant congenital heart defects.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470705	SCV002768602	likely benign	Congenital heart disease	2020-06-11	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.2, this variant is classified as likely benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with congenital heart disease. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine (exon 7). (I) 0251 - This variant is heterozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of congenital heart disease (gnomAD v2: 491 heterozygotes, 2 homozygotes). (SB) 0309 - An alternative amino acid change at the same position to tyrosine has been observed in gnomAD (v3) (1 heterozygote, 0 homozygote). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been classified mostly as benign or VUS in ClinVar. The pathogenic report in ClinVar is based on a publication in 2007 (PMID:18055909). (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
OMIM	RCV000009600	SCV000029818	pathogenic	Atrial septal defect 2	2007-12-01	no assertion criteria provided	literature only
OMIM	RCV000009601	SCV000029819	pathogenic	Tetralogy of Fallot	2007-12-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001794439	SCV002034137	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000431077	SCV002036476	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004018606	SCV004746067	likely benign	GATA4-related disorder	2023-04-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).