Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001326055 | SCV001517067 | uncertain significance | Developmental and epileptic encephalopathy, 30 | 2020-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 564 of the SIK1 protein (p.Leu564Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. 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. 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 SIK1 protein function. This variant has not been reported in the literature in individuals with SIK1-related conditions. This variant is present in population databases (rs746480237, ExAC 0.002%). |
| Ambry Genetics | RCV004960777 | SCV005501310 | likely benign | Inborn genetic diseases | 2024-08-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |