Submissions for variant NM_005257.6(GATA6):c.1342C>T (p.His448Tyr)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002472115	SCV002768525	uncertain significance	Atrial septal defect 9	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_005257.5(GATA6):c.1342C>T in exon 4 of 7 of the GATA6 gene. This substitution is predicted to create a moderate amino acid change from histidine to tyrosine at position 448 of the protein, NP_005248.2(GATA6):p.(His448Tyr). The histidine at this position has moderate conservation (100 vertebrates, UCSC), and is located within the GATA-type 2 zinc finger functional domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.00071% (2 heterozygotes). An alternative residue change at the same location has also been reported in the gnomAD database at a frequency of 0.00040%. The variant has not been previously reported in a clinical testing setting. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).