ClinVar Miner

Submissions for variant NM_020821.3(VPS13C):c.4165G>C (p.Gly1389Arg)

dbSNP: rs369100678
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Brain and Spine Institute, INSERM RCV000236463 SCV000262819 pathogenic Parkinson disease 2015-11-16 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017487 SCV004848452 likely pathogenic Young-onset Parkinson disease 2020-08-11 criteria provided, single submitter clinical testing The p.Gly1389Arg variant in VPS13C has been reported in 1 compound heterozygous individual with Parkinson disease (Lesage 2016 PMID: 26942284) and was absent from large population studies. It has also been reported in ClinVar (Variation ID 222070). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In addition, this variant is located in the first base of the exon, which is part of the 5’ splice region. Computational tools do not predict a splicing impact; however, RNA studies using patient's lymphocytes suggest a splicing impact (Lesage 2016 PMID: 26942284). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive parkinsonism. ACMG/AMP Criteria applied: PM2, PM3, PP3, PS3_Supporting.
GeneDx RCV005252811 SCV005906416 likely pathogenic not provided 2024-10-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Published functional studies demonstrate splicing is altered with the inclusion of 14bp from intron 37 (PMID: 26942284); This variant is associated with the following publications: (PMID: 28733970, 37991125, 34295884, 29288112, 26942284)
OMIM RCV000210217 SCV000266250 pathogenic Autosomal recessive early-onset Parkinson disease 23 2019-12-20 no assertion criteria provided literature only

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