ClinVar

Description

Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 4-5 in the OTOF gene. A presumed nomenclature of c.(227+1_228-1)_(509+1_510-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large in-frame deletion change in the OTOF gene, and affects the first C2 domain of the encoded protein (IPR000008). The variant was absent in 21694 control chromosomes in gnomAD database, structural variants data set. To our knowledge, no occurrence of c.(227+1_228-1)_(509+1_510-1)del in individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 9 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Missense variants in the overlapping deleted region (p.R82H, p.R69W) are reported in patients affected with hearing loss (PMID 31152317, PMID 34837038). Based on the evidence outlined above, the variant was classified as likely pathogenic.