Submissions for variant NM_153026.3(PRICKLE1):c.853A>C (p.Lys285Gln)

dbSNP: rs1555230175

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519556	SCV000617908	uncertain significance	not provided	2015-12-03	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PRICKLE1 gene. The K285Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K285Q 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 in mammals. 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.
Invitae	RCV000792650	SCV000931959	uncertain significance	Epilepsy, progressive myoclonic, 1B	2023-08-17	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 285 of the PRICKLE1 protein (p.Lys285Gln). This variant is not present in population databases (gnomAD no frequency). 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: 449601). 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.