Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000655347 | SCV000777277 | uncertain significance | Progressive myoclonic epilepsy type 5 | 2022-09-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PRICKLE2-related conditions. This variant is present in population databases (rs200223474, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 665 of the PRICKLE2 protein (p.Met665Thr). ClinVar contains an entry for this variant (Variation ID: 544243). 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 PRICKLE2 protein function. |
| Ambry Genetics | RCV002536306 | SCV003661943 | uncertain significance | Inborn genetic diseases | 2022-11-18 | criteria provided, single submitter | clinical testing | The c.1994T>C (p.M665T) alteration is located in exon 8 (coding exon 7) of the PRICKLE2 gene. This alteration results from a T to C substitution at nucleotide position 1994, causing the methionine (M) at amino acid position 665 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |