ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.328+4A>C (rs535970426)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766727 SCV000590033 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing The c.328+4A>C variant in the OTOG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Some splice predictor models indicate that this sequence change may damage the natural splice donor site in intron 3, which may cause abnormal gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The c.328+4A>C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.328+4A>C as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000497858 SCV000731754 uncertain significance not specified 2017-07-25 criteria provided, single submitter clinical testing The c.328+4A>C variant in OTOG has not been previously reported in individuals w ith hearing loss, but has been identified in 10/24674 of Latino chromosomes and 17/66944 of European chromosomes by the Genome Aggregation Database (gnomAD, htt p://; dbSNP rs535970426). Although this variant has be en seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is located in the 5' splice reg ion. Computational tools suggest a possible impact to splicing. However, this in formation is not predictive enough to determine out pathogenicity. In summary, t he clinical significance of the c.328+4A>C variant is uncertain.

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