ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.328+4A>C (rs535970426)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766727 SCV000590033 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing The c.328+4A>C variant in the OTOG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Some splice predictor models indicate that this sequence change may damage the natural splice donor site in intron 3, which may cause abnormal gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The c.328+4A>C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.328+4A>C as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000497858 SCV000731754 uncertain significance not specified 2017-07-25 criteria provided, single submitter clinical testing The c.328+4A>C variant in OTOG has not been previously reported in individuals w ith hearing loss, but has been identified in 10/24674 of Latino chromosomes and 17/66944 of European chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org/; dbSNP rs535970426). Although this variant has be en seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is located in the 5' splice reg ion. Computational tools suggest a possible impact to splicing. However, this in formation is not predictive enough to determine out pathogenicity. In summary, t he clinical significance of the c.328+4A>C variant is uncertain.

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.