Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001048558 | SCV001212571 | uncertain significance | Developmental and epileptic encephalopathy, 30 | 2025-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 663 of the SIK1 protein (p.Leu663Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SIK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 845487). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SIK1 protein function with a negative predictive value of 95%. 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 | RCV004031515 | SCV004948338 | uncertain significance | Inborn genetic diseases | 2021-08-13 | criteria provided, single submitter | clinical testing | The c.1989A>C (p.L663F) alteration is located in exon 14 (coding exon 13) of the SIK1 gene. This alteration results from a A to C substitution at nucleotide position 1989, causing the leucine (L) at amino acid position 663 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |