ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.5288G>A (p.Arg1763His) (rs185432248)

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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, Partners HealthCare Personalized Medicine RCV000223365 SCV000270669 likely benign not specified 2017-07-25 criteria provided, single submitter clinical testing p.Arg1763His in exon 35 of OTOG: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, >20 mammals have a Histidine (His) 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 been identified in 0.16% ( 105/66772) of European chromosomes by the Genome Aggregation Database (gnomAD, h ttp://gnomad.broadinstitute.org; dbSNP rs185432248).
Invitae RCV001346833 SCV001541067 uncertain significance not provided 2020-06-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1763 of the OTOG protein (p.Arg1763His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs185432248, ExAC 0.3%). This variant has not been reported in the literature in individuals with OTOG-related conditions. ClinVar contains an entry for this variant (Variation ID: 227784). 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 histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV001346833 SCV001779474 likely benign not provided 2021-05-20 criteria provided, single submitter clinical testing

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