ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.7418del (p.Arg2473fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089570 SCV001244775 likely pathogenic Deafness, autosomal recessive 18b 2018-07-18 criteria provided, single submitter clinical testing A homozygous frameshift deletion variant, NM_001277269.1(OTOG):c.7454delG, has been identified in exon 43 of 55 of the OTOG gene. This deletion is predicted to create a frameshift starting at amino acid position 2485, introducing a stop codon 77 residues downstream (NP_001264198.1(OTOG):p.(Arg2485Hisfs*77)). This variant is predicted to result in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. However, truncation of the protein as a result of a NMD-escape mechanism has not been excluded. The variant is present in the gnomAD database at a frequency of 0.02% (36 heterozygotes). This variant has not been previously reported in clinical cases. However, multiple variants resulting in a premature stop-codon upstream of this variant have been previously reported as pathogenic in individuals with autosomal recessive deafness (Yu, S. et al. (2018), Schraders, M. et al. (2012), ClinVar, HGMD). Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.

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