Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519106 | SCV000616970 | uncertain significance | not provided | 2016-11-08 | criteria provided, single submitter | clinical testing | The de novo D482N variant in the PRICKLE1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D482N variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The D482N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D482N as a variant of uncertain significance. |
Invitae | RCV001232568 | SCV001405130 | uncertain significance | Epilepsy, progressive myoclonic, 1B | 2022-10-13 | criteria provided, single submitter | clinical testing | 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 expected to disrupt PRICKLE1 protein function. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 482 of the PRICKLE1 protein (p.Asp482Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myoclonic epilepsy, developmental delay, and autism (PMID: 29790814). ClinVar contains an entry for this variant (Variation ID: 449153). |