ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.3229A>G (p.Ile1077Val)

gnomAD frequency: 0.00070  dbSNP: rs56359117
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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 RCV000612495 SCV000731780 likely benign not specified 2017-07-20 criteria provided, single submitter clinical testing p.Ile1089Val in exon 26 of OTOG: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 7 mammals have a valine (Val) at this position despite high nearby amino a cid conservation. In addition, computational prediction tools do not suggest a h igh likelihood of impact to the protein. It has also been identified in 0.2% (16 /8400) of Ashkenazi Jewish chromosomes and 0.07% (125/173696) of total chromosom es by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs56359117).
Labcorp Genetics (formerly Invitae), Labcorp RCV001868089 SCV002277595 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1089 of the OTOG protein (p.Ile1089Val). This variant is present in population databases (rs56359117, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. 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: 517484).
PreventionGenetics, part of Exact Sciences RCV003945553 SCV004758600 likely benign OTOG-related disorder 2022-12-01 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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