Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188747 | SCV000242371 | uncertain significance | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PRICKLE1 gene. The W516S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The W516S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The W516S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, 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. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Labcorp Genetics |
RCV000467028 | SCV000551464 | uncertain significance | Epilepsy, progressive myoclonic, 1B | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 516 of the PRICKLE1 protein (p.Trp516Ser). This variant is present in population databases (rs139901494, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PRICKLE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206670). 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 PRICKLE1 protein function. 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 | RCV004020288 | SCV000848693 | uncertain significance | not specified | 2024-03-21 | criteria provided, single submitter | clinical testing | The c.1547G>C (p.W516S) alteration is located in exon 7 (coding exon 6) of the PRICKLE1 gene. This alteration results from a G to C substitution at nucleotide position 1547, causing the tryptophan (W) at amino acid position 516 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |