ClinVar Miner

Submissions for variant NM_001308093.3(GATA4):c.934C>T (p.Arg312Trp)

dbSNP: rs138404762
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001339988 SCV001533774 uncertain significance Atrioventricular septal defect 4 2024-11-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 311 of the GATA4 protein (p.Arg311Trp). This variant is present in population databases (rs138404762, gnomAD 0.003%). This missense change has been observed in individual(s) with congenital heart defects (PMID: 27391137). ClinVar contains an entry for this variant (Variation ID: 1036914). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GATA4 protein function. Experimental studies have shown that this missense change affects GATA4 function (PMID: 27391137). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002224067 SCV002503392 uncertain significance not provided 2020-06-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004758790 SCV005366190 uncertain significance GATA4-related disorder 2024-03-21 no assertion criteria provided clinical testing The GATA4 c.931C>T variant is predicted to result in the amino acid substitution p.Arg311Trp. This variant has been reported in a family with congenital heart disease and co-segregated with affected individuals (Zhang et al. 2016. PubMed ID: 27391137). Further functional analyses showed that this variant inhibited the downstream activation of the GATA4 target gene (Zhang et al. 2016. PubMed ID: 27391137). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD. 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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