Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000792412 | SCV000931709 | uncertain significance | not provided | 2025-01-27 | 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 1665 of the SZT2 protein (p.Arg1665His). This variant is present in population databases (rs562214305, gnomAD 0.05%). 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: 433090). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SZT2 protein function with a positive predictive value of 80%. 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. |
Bioinformatics Core, |
RCV000655973 | SCV000588249 | pathogenic | Self-limited epilepsy with centrotemporal spikes | 2017-01-01 | no assertion criteria provided | case-control | CAADphred>15 |
Prevention |
RCV004748790 | SCV005362113 | uncertain significance | SZT2-related disorder | 2024-07-24 | no assertion criteria provided | clinical testing | The SZT2 c.4994G>A variant is predicted to result in the amino acid substitution p.Arg1665His. This variant has been reported in the heterozygous state in an individual from a exome-wide survey of individuals with typical and atypical Rolandic epilepsy; no additional studies were performed to assess its pathogenicity (Supplemental Table 1, Bobbili et al. 2018. PubMed ID: 29358611). This variant is reported in 0.049% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |