Submissions for variant NM_001365999.1(SZT2):c.9260A>G (p.His3087Arg)

gnomAD frequency: 0.00013  dbSNP: rs758905735

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000807157	SCV000947197	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 3030 of the SZT2 protein (p.His3030Arg). This variant is present in population databases (rs758905735, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SZT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 651736). 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 not expected to disrupt SZT2 protein function. 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.
GeneDx	RCV000807157	SCV001997436	uncertain significance	not provided	2023-08-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002442699	SCV002682834	uncertain significance	Inborn genetic diseases	2017-06-15	criteria provided, single submitter	clinical testing	The p.H3030R variant (also known as c.9089A>G), located in coding exon 65 of the SZT2 gene, results from an A to G substitution at nucleotide position 9089. The histidine at codon 3030 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV001788355	SCV004178066	uncertain significance	Developmental and epileptic encephalopathy, 18	2023-04-11	criteria provided, single submitter	clinical testing
GenomeConnect - Brain Gene Registry	RCV001788355	SCV002030763	not provided	Developmental and epileptic encephalopathy, 18		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 08-24-2021 by Lab or GTR ID 500031. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR ) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator John Constantino MD PhD from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect.