ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.4012C>T (p.Arg1338Trp)

gnomAD frequency: 0.00076  dbSNP: rs61734125
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Total submissions: 6
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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 RCV000218219 SCV000270662 likely benign not specified 2016-02-23 criteria provided, single submitter clinical testing p.Arg1350Trp in exon 32 of OTOG: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals, sug gesting that variants at this position are tolerated. Of note, 2 mammals (marmos et and Bactrian camel) have a Tryptophan (Trp) at this position. In addition, c omputational prediction tools do not suggest a high likelihood of impact to the protein. The variant has been reported in 1/920 African chromosomes by the Exome Aggregate Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs61734125).
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000443155 SCV000510752 uncertain significance not provided 2017-01-24 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
GeneDx RCV000443155 SCV001791996 uncertain significance not provided 2022-06-08 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 RCV000443155 SCV002188038 uncertain significance not provided 2022-10-25 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 1350 of the OTOG protein (p.Arg1350Trp). This variant is present in population databases (rs61734125, gnomAD 0.2%). 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: 227777). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; 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.
Revvity Omics, Revvity RCV001824689 SCV004235699 uncertain significance Autosomal recessive nonsyndromic hearing loss 18B 2023-11-02 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV001824689 SCV002075122 not provided Autosomal recessive nonsyndromic hearing loss 18B no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 04-26-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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