ClinVar Miner

Submissions for variant NM_001308093.3(GATA4):c.851G>A (p.Arg284His)

dbSNP: rs180765750
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001330680 SCV001522432 likely pathogenic Atrial septal defect 2 2020-12-26 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV002546407 SCV003233229 pathogenic Atrioventricular septal defect 4 2022-11-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt GATA4 protein function. ClinVar contains an entry for this variant (Variation ID: 1029405). This missense change has been observed in individual(s) with congenital diaphragmatic hernia and/or syndromic structural heart defects (PMID: 15863664, 23138528, 23696316, 32719394). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 283 of the GATA4 protein (p.Arg283His).
Baylor Genetics RCV003147617 SCV003834851 likely pathogenic Testicular anomalies with or without congenital heart disease 2020-12-26 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004035700 SCV004111369 likely pathogenic GATA4-related disorder 2024-01-25 criteria provided, single submitter clinical testing The GATA4 c.848G>A variant is predicted to result in the amino acid substitution p.Arg283His. This variant was detected in an individual with subaortic ventricular septal defect with overriding aorta, septum primum defect, patent foramen ovale, and a common atrioventricular canal (Reamon-Buettner and Borlak 2005. PubMed ID: 15863664). The variant was detected in affected tissue but was absent in unaffected tissue of the same heart indicating the variant was mosaic variant (Reamon-Buettner and Borlak. 2005. PubMed ID: 15863664). Additionally, this variant was reported as de novo in a patient with congenital diaphragmatic hernia, septal defects, and neurodevelopmental delay (Yu et al. 2012. PubMed ID: 23138528; Table S3 - Qiao et al. 2020. PubMed ID: 32719394). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD; however, quality metrics at this site indicate it may not be a reliable estimate of population frequency. This variant is interpreted as likely pathogenic.

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