ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.391T>G (p.Leu131Val) (rs35731866)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000718412 SCV000849275 uncertain significance Seizures 2017-03-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000188726 SCV000242350 uncertain significance not provided 2018-03-23 criteria provided, single submitter clinical testing The L131V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L131V variant is observed in 38/30768 (0.1%) alleles from individuals of South Asian background (Lek et al., 2016). The L131V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter 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 RCV000525462 SCV000646883 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 131 of the PRICKLE1 protein (p.Leu131Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs35731866, ExAC 0.1%). This variant has not been reported in the literature in individuals with PRICKLE1-related disease. ClinVar contains an entry for this variant (Variation ID: 206652). 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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