ClinVar Miner

Submissions for variant NM_015243.2(VPS13B):c.560G>A (p.Arg187His) (rs150941426)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658167 SCV000779938 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing The R187H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R187H variant is observed in 13/30782 (0.04%) alleles from individuals of South Asian background (Lek et al., 2016). The R187H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000501218 SCV000597911 uncertain significance not specified 2015-11-19 criteria provided, single submitter clinical testing
Invitae RCV000821626 SCV000962395 uncertain significance Cohen syndrome 2018-09-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 187 of the VPS13B protein (p.Arg187His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs150941426, ExAC 0.05%). This variant has not been reported in the literature in individuals with VPS13B-related disease. ClinVar contains an entry for this variant (Variation ID: 437253). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.