Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001314617 | SCV001505153 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1098 of the SPTAN1 protein (p.Arg1098Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SPTAN1-related conditions (PMID: 35150594). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1015715). 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 SPTAN1 protein function. This variant disrupts the p.Arg1098 amino acid residue in SPTAN1. Other variant(s) that disrupt this residue have been observed in individuals with SPTAN1-related conditions (PMID: 34590414), which suggests that this may be a clinically significant amino acid residue. 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. |
Molecular Genetics Lab, |
RCV003883176 | SCV004697679 | uncertain significance | Developmental and epileptic encephalopathy, 5 | criteria provided, single submitter | clinical testing | ||
Solve- |
RCV003883176 | SCV005091513 | likely pathogenic | Developmental and epileptic encephalopathy, 5 | 2022-06-01 | no assertion criteria provided | provider interpretation | Variant confirmed as disease-causing by referring clinical team |