ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.1544T>C (p.Ile515Thr) (rs80356586)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000604852 SCV000710845 likely pathogenic Rare genetic deafness 2017-02-14 criteria provided, single submitter clinical testing The p.Ile515Thr (NM_194248.2 c.1544T>C, ClinVar Variation ID#6143) variant in OT OF has been reported in 1 compound heterozygous individual with hearing loss who had a temperature-sensitive auditory neuropathy phenotype, in trans with a nons ense variant, and segregated with disease in an affected family member (Varga 20 06, Strenzke 2016, Avraham 2016). This variant has also been reported in 1 homoz ygous individual with hearing loss and in 3 affected homozygous family members, who all had a second missense OTOF variant of uncertain significance in cis (Mir ghomizadeh 2002). A knock-in mouse model homozygous for the p.Ile515Thr variant was shown to have hearing loss (Strenzke 2016). This variant has also been ident ified in 0.002% (1/65,772) of European chromosomes by the Exome Aggregation Cons ortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80356586). Although this v ariant has been seen in the general population, its frequency is low enough to b e consistent with a recessive carrier frequency. In summary, although additional studies are required to fully establish its clinical significance, the p.Ile515 Thr variant is likely pathogenic for OTOF-related hearing loss in an autosomal r ecessive manner based upon biallelic observations in patients, low frequency in controls, and an animal model.
OMIM RCV000006517 SCV000026700 pathogenic Auditory neuropathy, autosomal recessive, 1 2006-07-01 no assertion criteria provided literature only
GeneReviews RCV000021035 SCV000041689 association Deafness, autosomal recessive 9 2015-07-30 no assertion criteria provided literature only
OMIM RCV000021035 SCV000222658 pathogenic Deafness, autosomal recessive 9 2006-07-01 no assertion criteria provided literature only

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.