ClinVar Miner

Submissions for variant NM_001308093.3(GATA4):c.392C>G (p.Ala131Gly)

gnomAD frequency: 0.00019  dbSNP: rs1013984246
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493402 SCV000581885 uncertain significance not provided 2022-12-21 criteria provided, single submitter clinical testing Reported as a de novo variant in a patient with upper limb defects and no congenital heart defects (Porto et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21637475, 35047139)
Invitae RCV001053521 SCV001217788 uncertain significance Atrioventricular septal defect 4 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 131 of the GATA4 protein (p.Ala131Gly). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with isolated hand anomalies (PMID: 21637475). ClinVar contains an entry for this variant (Variation ID: 429341). 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 with a negative predictive value of 80%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224301 SCV003920002 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 2021-03-30 criteria provided, single submitter clinical testing GATA4 NM_002052.5 exon 2 p.Ala131Gly (c.392C>G): This variant has been reported in the literature in one individual with isolated limb malformations but no evidence of cardiac disease on echo or ECG (Porto 2010 PMID:21637475). This variant is present in 0.003% (1/30376) of total alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/8-11566213-C-G) and is present in ClinVar (Variation ID:429341). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Baylor Genetics RCV003458166 SCV004183533 uncertain significance Testicular anomalies with or without congenital heart disease 2023-09-24 criteria provided, single submitter clinical testing

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