ClinVar Miner

Submissions for variant NM_001308093.3(GATA4):c.1210C>A (p.Leu404Met)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV004364463 SCV004114224 uncertain significance GATA4-related disorder 2022-10-10 criteria provided, single submitter clinical testing The GATA4 c.1207C>A variant is predicted to result in the amino acid substitution p.Leu403Met. This variant has been reported in individuals with sporadic hypoplastic right ventricle and atrial septal defect-ventricular septal defect (ASD-VSD) (Rajagopal et al. 2007. PubMed ID: 17643447; Dinesh et al. 2011. PubMed ID: 21631294). Structural analysis of the protein determined that this variant impacts structure (Dinesh et al. 2011. PubMed ID: 21631294). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-11615862-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003528470 SCV004291402 uncertain significance Atrioventricular septal defect 4 2024-03-20 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 403 of the GATA4 protein (p.Leu403Met). This variant is present in population databases (rs777778466, gnomAD 0.02%). This missense change has been observed in individual(s) with GATA4-related conditions (PMID: 17643447, 21631294). ClinVar contains an entry for this variant (Variation ID: 2637134). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GATA4 function (PMID: 35418170). 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.

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