ClinVar Miner

Submissions for variant NM_001308093.3(GATA4):c.942G>T (p.Glu314Asp)

gnomAD frequency: 0.00009  dbSNP: rs372407808
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557722 SCV000652013 uncertain significance Atrioventricular septal defect 4 2023-08-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 313 of the GATA4 protein (p.Glu313Asp). This variant is present in population databases (rs372407808, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GATA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 472784). 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 not expected to disrupt GATA4 protein function. 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.
GeneDx RCV001540479 SCV001758370 uncertain significance not provided 2023-02-23 criteria provided, single submitter clinical testing Identified in a patient with bicuspid aortic valve (BAV) in published literature (Musfee et al., 2020); reported as p.(Glu314Asp) due to alternate nomenclature; 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: 27374936, 32748548)
Fulgent Genetics, Fulgent Genetics RCV002506364 SCV002814296 uncertain significance Atrial septal defect 2; Tetralogy of Fallot; Ventricular septal defect 1; Atrioventricular septal defect 4; Testicular anomalies with or without congenital heart disease 2021-07-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004024214 SCV004118027 uncertain significance GATA4-related disorder 2022-11-06 criteria provided, single submitter clinical testing The GATA4 c.939G>T variant is predicted to result in the amino acid substitution p.Glu313Asp. This variant has been reported in a cohort study of adults with bicuspid aortic valve (reported as p.Glu314Asp in Musfee et al. 2020. PubMed ID: 32748548). This variant is reported in 0.020% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-11612584-G-T), which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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