ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.2453G>A (p.Arg818Gln)

gnomAD frequency: 0.00002  dbSNP: rs748844952
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Total submissions: 3
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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 RCV000825416 SCV000966714 uncertain significance not specified 2018-12-04 criteria provided, single submitter clinical testing The p.Arg818Gln variant in OTOF has not been previously reported in individuals with hearing loss or auditory neuropathy spectrum disorder, but has been identif ied in 0.003% (4/109134) of European chromosomes by gnomAD (http://gnomad.broadi nstitute.org). Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, the c linical significance of the p.Arg818Gln variant is uncertain. ACMG/AMP Criteria applied: PM2.
Invitae RCV001858391 SCV002205625 uncertain significance not provided 2021-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 818 of the OTOF protein (p.Arg818Gln). This variant is present in population databases (rs748844952, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 666895). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV003243351 SCV003942443 uncertain significance Inborn genetic diseases 2023-04-11 criteria provided, single submitter clinical testing The c.2453G>A (p.R818Q) alteration is located in exon 21 (coding exon 21) of the OTOF gene. This alteration results from a G to A substitution at nucleotide position 2453, causing the arginine (R) at amino acid position 818 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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