ClinVar Miner

Submissions for variant NM_017890.5(VPS13B):c.4186C>T (p.Gln1396Ter)

gnomAD frequency: 0.00001  dbSNP: rs559590419
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
Counsyl RCV000668515 SCV000793133 uncertain significance Cohen syndrome 2017-07-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668515 SCV001592713 pathogenic Cohen syndrome 2023-11-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1396*) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is present in population databases (rs559590419, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 553132). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV000668515 SCV002073145 likely pathogenic Cohen syndrome criteria provided, single submitter clinical testing The stop gained p.Q1396* in VPS13B (NM_017890.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Q1396* variant is observed in 2/30,612 (0.0065%) alleles from individuals of South Asian background in gnomAD Exomes and in 1/978 (0.1022%) alleles from individuals of South Asian background in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been reported previously to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.

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.