Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003069196 | SCV003466194 | uncertain significance | not provided | 2022-10-17 | 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. 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. This variant has not been reported in the literature in individuals affected with SZT2-related conditions. This variant is present in population databases (rs774830511, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 482 of the SZT2 protein (p.Arg482Cys). |
Department of Developmental Neurology, |
RCV003444350 | SCV004100906 | not provided | Developmental and epileptic encephalopathy, 18 | no assertion provided | phenotyping only | The c.1444C>T, p.(Arg482Cys) variant locates in exon 10 of SZT2 gene. There are 3 individuals heterozygous for the variant in the Genome Aggregation Database (gnomAD, n>120,000 exomes and >15,000 genomes). Database curators have made every effort to exclude individuals with severe pediatric diseases from these cohorts. Arginine is a weakly conserved amino acid and there is a large physicochemical difference between arginine and cysteine. In silico tools PolyPhen and MutationTaster predict the variant as disease causing, whereas SIFT predicts it as tolerated. This variant was detected with another heterozygous variant c.4369C>T, p.(Arg1457Trp) in SZT2 gene in a child with epilepsy, psychomotor delay and autism spectrum disorder. However, parental samplese were not tested. |