Submissions for variant NM_001365999.1(SZT2):c.8039G>A (p.Arg2680His)

gnomAD frequency: 0.00013  dbSNP: rs144218947

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000500684	SCV000597381	uncertain significance	not specified	2015-10-16	criteria provided, single submitter	clinical testing
Invitae	RCV000822279	SCV000963074	uncertain significance	not provided	2022-09-12	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2623 of the SZT2 protein (p.Arg2623His). This variant is present in population databases (rs144218947, 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: 436933). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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	RCV000822279	SCV001818596	uncertain significance	not provided	2023-06-11	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	RCV002524305	SCV003684962	uncertain significance	Inborn genetic diseases	2021-09-01	criteria provided, single submitter	clinical testing	The c.7868G>A (p.R2623H) alteration is located in exon 57 (coding exon 57) of the SZT2 gene. This alteration results from a G to A substitution at nucleotide position 7868, causing the arginine (R) at amino acid position 2623 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000822279	SCV004123694	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SZT2: PM2
Genome-Nilou Lab	RCV003457714	SCV004177991	uncertain significance	Developmental and epileptic encephalopathy, 18	2023-04-11	criteria provided, single submitter	clinical testing