ClinVar Miner

Submissions for variant NM_198578.4(LRRK2):c.4321C>T (p.Arg1441Cys) (rs33939927)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000002015 SCV000640130 pathogenic Parkinson disease 8, autosomal dominant 2018-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1441 of the LRRK2 protein (p.Arg1441Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs33939927, ExAC 0.001%). This variant has been reported to segregate with Parkinson's disease (PD) in multiple families and has been reported in several PD cases (PMID: 15541309, 21538529, 24565865). ClinVar contains an entry for this variant (Variation ID: 1938). In vitro experimental studies have shown that this missense affects several aspects of LRRK2 function, including increasing auto-phosphorylation activity (PMID: 21658387, 23241745, 17200152), although one study was unable to reproduce this finding (PMID: 16750377). In addition, a mouse model carrying this variant recapitulates several aspects of disease (PMID: 21494637). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002015 SCV000022173 pathogenic Parkinson disease 8, autosomal dominant 2009-08-25 no assertion criteria provided literature only
GeneReviews RCV000002015 SCV000056116 pathologic Parkinson disease 8, autosomal dominant 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000002015 SCV000599864 pathogenic Parkinson disease 8, autosomal dominant 2017-04-20 no assertion criteria provided clinical testing

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