Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000800442 | SCV000940157 | uncertain significance | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1664 of the SZT2 protein (p.His1664Tyr). This variant is present in population databases (rs376678520, 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: 646206). 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 with a negative 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. |
| Ambry Genetics | RCV002534638 | SCV003695246 | uncertain significance | Inborn genetic diseases | 2021-12-03 | criteria provided, single submitter | clinical testing | The c.4990C>T (p.H1664Y) alteration is located in exon 35 (coding exon 35) of the SZT2 gene. This alteration results from a C to T substitution at nucleotide position 4990, causing the histidine (H) at amino acid position 1664 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Genome- |
RCV003457807 | SCV004180964 | uncertain significance | Developmental and epileptic encephalopathy, 18 | 2023-04-11 | criteria provided, single submitter | clinical testing |