ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.7658G>C (p.Arg2553Pro)

gnomAD frequency: 0.00026  dbSNP: rs563003848
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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 RCV000606922 SCV000731593 uncertain significance not specified 2017-04-13 criteria provided, single submitter clinical testing The p.Arg2565Pro variant in OTOG has not been previously reported in individuals with hearing loss, but has been identified in 13/24534 Latino chromosomes by th e Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP r s563003848). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predic tion tools and conservation analysis do not provide strong support for or agains t an impact to the protein. In summary, the clinical significance of the p.Arg25 65Pro variant is uncertain.
Baylor Genetics RCV001336341 SCV001529702 uncertain significance Autosomal recessive nonsyndromic hearing loss 18B 2018-01-30 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV002253533 SCV002525437 uncertain significance not provided 2022-06-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002253533 SCV003461401 uncertain significance not provided 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 2565 of the OTOG protein (p.Arg2565Pro). This variant is present in population databases (rs563003848, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with OTOG-related conditions. ClinVar contains an entry for this variant (Variation ID: 517352). 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: "Possibly Damaging"; 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.

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