ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.1145G>A (p.Arg382Lys) (rs748636455)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000712844 SCV000843381 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000188741 SCV000297383 uncertain significance not specified 2015-11-26 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000712844 SCV000336907 uncertain significance not provided 2015-11-11 criteria provided, single submitter clinical testing
GeneDx RCV000712844 SCV000242365 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRICKLE1 gene. The R382K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R382K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R382K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. 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 RCV000800273 SCV000939978 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 382 of the PRICKLE1 protein (p.Arg382Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs748636455, ExAC 0.01%). This variant has not been reported in the literature in individuals with PRICKLE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206664). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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