Submissions for variant NM_005257.6(GATA6):c.151G>T (p.Glu51Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002650876	SCV003515999	pathogenic	Atrioventricular septal defect 5	2022-07-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu51*) in the GATA6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATA6 are known to be pathogenic (PMID: 22158542, 24310933). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GATA6-related conditions. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003420385	SCV004114077	uncertain significance	GATA6-related disorder	2023-06-28	criteria provided, single submitter	clinical testing	The GATA6 c.151G>T variant is predicted to result in premature protein termination (p.Glu51*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in GATA6 are expected to be pathogenic, although none have been reported upstream of this position. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.