Submissions for variant NM_001277269.2(OTOG):c.[3719C>T] (rs117005078)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000214949	SCV000272248	benign	not specified	2017-06-13	criteria provided, single submitter	clinical testing	p.Pro1240Leu in exon 30 of OTOG: This variant is not expected to have clinical significance because it has been identified in 0.6% (384/67268) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs117005078). Furthermore, this variant has been reported by our la boratory in 10 individuals with hearing loss, including 4 with an alternate gene tic etiology identified.
GeneDx	RCV000214949	SCV000618434	uncertain significance	not specified	2017-08-01	criteria provided, single submitter	clinical testing	The P1240L variant in the OTOG gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 4/1240 (0.32%) alleles from individuals of Finnish background in the ExAC dataset, and has been observed in the homozygous state in one presumably unaffected individual undergoing testing at GeneDx (Lek et al., 2016). The P1240L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P1240L as a variant of uncertain significance.
Invitae	RCV000969361	SCV001116873	likely benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000969361	SCV001144840	likely benign	not provided	2018-09-12	criteria provided, single submitter	clinical testing