ClinVar Miner

Submissions for variant NM_018206.6(VPS35):c.1420C>G (p.Gln474Glu) (rs370401767)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807045 SCV000947073 uncertain significance Parkinson disease 17 2019-06-22 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 474 of the VPS35 protein (p.Gln474Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs370401767, ExAC 0.006%). This variant has not been reported in the literature in individuals with VPS35-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000807045 SCV001273913 benign Parkinson disease 17 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

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