Submissions for variant NM_005257.6(GATA6):c.595C>T (p.Pro199Ser)

gnomAD frequency: 0.00001  dbSNP: rs1428539753

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001344287	SCV001538328	uncertain significance	Atrioventricular septal defect 5	2020-10-07	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GATA6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces proline with serine at codon 199 of the GATA6 protein (p.Pro199Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine.
PreventionGenetics, part of Exact Sciences	RCV003416240	SCV004108075	uncertain significance	GATA6-related disorder	2023-01-18	criteria provided, single submitter	clinical testing	The GATA6 c.595C>T variant is predicted to result in the amino acid substitution p.Pro199Ser. 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. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.