ClinVar Miner

Submissions for variant NM_198578.4(LRRK2):c.3683G>C (p.Ser1228Thr) (rs60185966)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000032445 SCV000056102 unknown Parkinson disease 8, autosomal dominant 2012-09-13 no assertion criteria provided curation Converted during submission to Uncertain significance.
Invitae RCV000032445 SCV000832802 uncertain significance Parkinson disease 8, autosomal dominant 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 1228 of the LRRK2 protein (p.Ser1228Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs60185966, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with Parkinson disease and in control individuals (PMID: 16251215, 21885347). This variant has been observed to segregate with Parkinson disease in families (PMID: 16251215, Invitae). ClinVar contains an entry for this variant (Variation ID: 39171). Experimental studies have shown that this missense change does not have an effect on the kinase activity or the cellular localization of the LRRK2 protein (PMID: 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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