ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.959C>T (p.Ser320Leu)

gnomAD frequency: 0.00006  dbSNP: rs371666216
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825999 SCV000967487 uncertain significance not specified 2018-04-10 criteria provided, single submitter clinical testing The p.Ser320Leu variant in OTOF has not been previously reported in individuals with hearing loss, but has been identified in 11/126364 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs371666216). This variant is located in the last three bases of the exon, whic h is part of the 5? splice region. Computational tools do not predict altered sp licing. However, this information is not predictive enough to rule out pathogeni city. Additional computational prediction tools and conservation analysis do not provide strong support for or against an impact of the missense change on the p rotein. In summary, the clinical significance of the p.Ser320Leu variant is unce rtain. ACMG/AMP Criteria applied: none.
Invitae RCV001858411 SCV002184448 uncertain significance not provided 2021-09-03 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 320 of the OTOF protein (p.Ser320Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs371666216, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 667297). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.