ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.853A>C (p.Lys285Gln) (rs1555230175)

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Total submissions: 2
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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 Progressive myoclonus epilepsy with ataxia 2018-07-26 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 285 of the PRICKLE1 protein (p.Lys285Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PRICKLE1-related disease. ClinVar contains an entry for this variant (Variation ID: 449601). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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