ClinVar Miner

Submissions for variant NM_198578.4(LRRK2):c.6187_6191del (p.Leu2062_Leu2063insTer) (rs111739194)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000387933 SCV000335661 uncertain significance not provided 2015-10-01 criteria provided, single submitter clinical testing
GeneReviews RCV000032494 SCV000056157 unknown Parkinson disease 8, autosomal dominant 2012-09-13 no assertion criteria provided curation Converted during submission to Uncertain significance.
Invitae RCV000032494 SCV000829612 uncertain significance Parkinson disease 8, autosomal dominant 2018-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2063*) in the LRRK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs577018258, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Parkinson's disease, an individual affected with dementia, and in 2 unaffected individuals (PMID: 24821816, 21885347, 29859640). ClinVar contains an entry for this variant (Variation ID: 39220). Experimental studies have shown that this nonsense change does not significantly reduce kinase activity, but does reduce cell survival rates (PMID: 25821816). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LRRK2 cause disease. 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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