Submissions for variant NM_001365999.1(SZT2):c.9938C>T (p.Ala3313Val)

gnomAD frequency: 0.00006  dbSNP: rs201695619

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000816288	SCV000956789	uncertain significance	not provided	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3256 of the SZT2 protein (p.Ala3256Val). This variant is present in population databases (rs201695619, gnomAD 0.2%). 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: 659302). 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. 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	RCV000816288	SCV002758795	uncertain significance	not provided	2022-06-03	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
Genome-Nilou Lab	RCV003457831	SCV004178112	uncertain significance	Developmental and epileptic encephalopathy, 18	2023-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955525	SCV004771203	likely benign	SZT2-related condition	2022-04-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).