Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001054010 | SCV001218301 | uncertain significance | Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates | 2023-03-08 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Asn80 amino acid residue in STIM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25326555). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 STIM1 protein function. ClinVar contains an entry for this variant (Variation ID: 849947). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. This variant is present in population databases (rs748277951, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 80 of the STIM1 protein (p.Asn80Ser). 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. |