Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002318012 | SCV000849598 | uncertain significance | Inborn genetic diseases | 2021-12-10 | criteria provided, single submitter | clinical testing | The c.2033A>C (p.Q678P) 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 2033, causing the glutamine (Q) at amino acid position 678 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001369004 | SCV001565430 | uncertain significance | Developmental and epileptic encephalopathy, 30 | 2024-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 678 of the SIK1 protein (p.Gln678Pro). This variant is present in population databases (rs763160252, gnomAD 0.008%). 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: 589068). 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. |
Breakthrough Genomics, |
RCV004692209 | SCV005195158 | uncertain significance | not provided | criteria provided, single submitter | not provided |