Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002234951 | SCV000943078 | uncertain significance | Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 520 of the STIM1 protein (p.Asp520Asn). This variant is present in population databases (rs199914458, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 648477). 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 STIM1 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 | RCV004669126 | SCV005165416 | uncertain significance | Inborn genetic diseases | 2024-06-07 | criteria provided, single submitter | clinical testing | The c.1558G>A (p.D520N) alteration is located in exon 12 (coding exon 12) of the STIM1 gene. This alteration results from a G to A substitution at nucleotide position 1558, causing the aspartic acid (D) at amino acid position 520 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |