ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.4246C>T (p.Arg1416Trp)

gnomAD frequency: 0.00048  dbSNP: rs559512010
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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 RCV000602749 SCV000712568 likely benign not specified 2016-10-25 criteria provided, single submitter clinical testing p.Arg1428Trp in exon 33 of OTOG: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, >10 mammals have a tryptophan (Trp) at this position despite high nearby a mino acid conservation. In addition, computational prediction tools do not sugge st a high likelihood of impact to the protein. It has also been identified in 1/ 820 African and 1/4346 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs559512010).
GeneDx RCV001775914 SCV002013248 uncertain significance not provided 2024-06-17 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001775914 SCV002158758 uncertain significance not provided 2022-05-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1428 of the OTOG protein (p.Arg1428Trp). This variant is present in population databases (rs559512010, gnomAD 0.08%). 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: 505385). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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