Submissions for variant NM_001277269.1(OTOG):c.4693G>T (p.Gly1565Ter) (rs897822685)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000600685	SCV000731383	likely pathogenic	Rare genetic deafness	2017-01-24	criteria provided, single submitter	clinical testing	The p.Gly1565X variant in OTOG has not been previously reported in individuals w ith hearing loss or in large population databases. This nonsense variant leads t o a premature termination codon at position 1565, which is predicted to lead to a truncated or absent protein. Two loss of function variants in the OTOG gene ha ve been reported to segregate with hearing loss in two families (Schraders 2012) . Furthermore, disruption of Otog in mice results in deafness, supporting a loss -of-function mechanism for the disease (Simmler 2000). In summary, while the p.G ly1565X variant is likely pathogenic for autosomal recessive nonsyndromic hearin g loss based on the predicted impact of the variant, additional evidence support ing the role of OTOG in hearing loss is needed to definitively establish the cli nical significance of this variant.
GeneDx	RCV000760670	SCV000890562	likely pathogenic	not provided	2021-06-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 10655058, 23122587)