ClinVar Miner

Submissions for variant NM_198578.3(LRRK2):c.632C>T (p.Ala211Val) (rs112794616)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000032497 SCV000056160 unknown Parkinson disease 8, autosomal dominant 2012-09-13 no assertion criteria provided curation Converted during submission to Uncertain significance.
Invitae RCV000032497 SCV000762635 uncertain significance Parkinson disease 8, autosomal dominant 2018-01-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 211 of the LRRK2 protein (p.Ala211Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs112794616, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with Parkinson disease (PMID: 17222106, 21885347, 19405094, 29248340) as well as in unaffected individuals (PMID: 19405094, 21885347). ClinVar contains an entry for this variant (Variation ID: 39223). Experimental studies have shown that this missense change results in a modest increase in kinase activity and increased FADD-dependent apoptotic death in culterured neurons (PMID: 27832104, 20642453). 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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