ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.6092C>T (p.Thr2031Ile)

gnomAD frequency: 0.00035  dbSNP: rs545321215
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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 RCV000825216 SCV000966496 likely benign not specified 2018-05-15 criteria provided, single submitter clinical testing p.Thr2043Ile in exon 35 of OTOG: This variant is likely benign because it is not conserved through species, with 4 mammals (dog, panda, Pacific walrus and Wedde ll seal) having an isoleucine (Ile) at this position. It has been identified in 0.066% (43/64788) of European chromosomes by the Genome Aggregation Database (gn omAD, http://gnomad.broadinstitute.org; dbSNP rs545321215). ACMG/AMP criteria a pplied: BP4_Strong.
GeneDx RCV001567834 SCV001791597 uncertain significance not provided 2021-08-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001567834 SCV002215237 uncertain significance not provided 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2043 of the OTOG protein (p.Thr2043Ile). This variant is present in population databases (rs545321215, gnomAD 0.07%). 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: 666739). 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 isoleucine 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.
PreventionGenetics, part of Exact Sciences RCV003928293 SCV004739155 uncertain significance OTOG-related condition 2024-01-02 criteria provided, single submitter clinical testing The OTOG c.6128C>T variant is predicted to result in the amino acid substitution p.Thr2043Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.063% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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