Submissions for variant NM_194248.3(OTOF):c.3913AAG[7] (p.Lys1310dup)

dbSNP: rs368148603

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214082	SCV000272239	uncertain significance	not specified	2016-03-22	criteria provided, single submitter	clinical testing	The p.Lys1310dup variant in OTOF has been previously reported in one individual with hearing loss and multiple congenital anomalies who was compound heterozygou s for a second likely pathogenic variant in OTOF (Lee 2014). This variant has a lso been identified in 6/8612 of East Asian chromosomes and 8/16414 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs768338261). Although this variant has been seen in the general po pulation, its frequency is not high enough to rule out a pathogenic role. This v ariant results in an in-frame insertion of one lysine (Lys) residue in a lysine tract and does not alter the amino acid reading frame. It is unclear if this ins ertion will impact the protein. In summary, the clinical significance of the p.L ys1310dup variant is uncertain.
GeneDx	RCV001788087	SCV002030868	uncertain significance	not provided	2022-11-15	criteria provided, single submitter	clinical testing	Identified with a second OTOF variant in unrelated patients with hearing loss in published literature, however, information regarding presence or absence of auditory neuropathy was not provided (Lee et al., 2014; Liu et al., 2022); In-frame insertion of one amino acid in a repetitive region with no known function; This variant is associated with the following publications: (PMID: 34426522, 35114279, 25326637)
Fulgent Genetics, Fulgent Genetics	RCV002485397	SCV002779373	uncertain significance	Autosomal recessive nonsyndromic hearing loss 9	2022-04-28	criteria provided, single submitter	clinical testing
Invitae	RCV001788087	SCV003461262	uncertain significance	not provided	2022-06-19	criteria provided, single submitter	clinical testing	This variant, c.3928_3930dup, results in the insertion of 1 amino acid(s) of the OTOF protein (p.Lys1310dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768338261, gnomAD 0.08%). This variant has been observed in individual(s) with clinical features of OTOF-related conditions (PMID: 25326637). ClinVar contains an entry for this variant (Variation ID: 229079). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.