ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.5407GAG[1] (p.Glu1804del)

dbSNP: rs397515607
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000211735 SCV000206326 likely pathogenic Rare genetic deafness 2014-07-03 criteria provided, single submitter clinical testing The Glu1804del variant in OTOF has been reported in 3 siblings with temperature- sensitive auditory neuropathy (Marlin 2010). All three affected siblings were ho mozygous and their unaffected parents were heterozygous for this variant. This v ariant has also been identified by our laboratory in trans with another pathogen ic variant in OTOF in an individual with auditory neuropathy. It has not been id entified in large population studies. This variant causes an in-frame deletion o f a glutamate (Glu) at position 1804, which is highly conserved in mammals and e volutionary distant species, suggesting that a change at this position may not b e tolerated, though this information is not predictive enough to determine patho genicity. In summary, although additional studies are required to fully establi sh its clinical significance, this variant is likely pathogenic.
GeneDx RCV004719687 SCV005324880 likely pathogenic not provided 2024-01-10 criteria provided, single submitter clinical testing In-frame deletion of one amino acid in a non-repeat region; Not observed in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33256196, 36837553, 34692690, 37679651, 20230791)
Labcorp Genetics (formerly Invitae), Labcorp RCV004719687 SCV005834792 uncertain significance not provided 2024-11-12 criteria provided, single submitter clinical testing This variant, c.5410_5412del, results in the deletion of 1 amino acid(s) of the OTOF protein (p.Glu1804del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with OTOF-related conditions (PMID: 20230791). It has also been observed to segregate with disease in related individuals. 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.
GeneReviews RCV000056050 SCV000087110 not provided Autosomal recessive nonsyndromic hearing loss 9 no assertion provided literature only

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