Submissions for variant NM_194323.3(OTOF):c.3514C>T (p.Arg1172Trp)

gnomAD frequency: 0.00001  dbSNP: rs530821443

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861898	SCV002180632	uncertain significance	not provided	2021-11-17	criteria provided, single submitter	clinical testing	The OTOF gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_194323.2, and corresponds to NM_194248.2:c.*19C>T in the primary transcript. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1172 of the OTOF protein (p.Arg1172Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with OTOF-related conditions (PMID: 19250381, 30303587; Invitae). This variant is also known as c.5815C>T (p.R1939W). ClinVar contains an entry for this variant (Variation ID: 562079). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Arg1172 amino acid residue in OTOF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12525542, 26632695). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
National Institute on Deafness and Communication Disorders, National Institutes of Health	RCV000681532	SCV000807724	pathogenic	Autosomal recessive nonsyndromic hearing loss 9	2018-07-05	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291227	SCV001479652	likely pathogenic	Hearing loss, autosomal recessive		no assertion criteria provided	research
Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University	RCV003984846	SCV004801099	likely pathogenic	Auditory neuropathy spectrum disorder	2020-08-01	no assertion criteria provided	clinical testing