Submissions for variant NM_001277269.1(OTOG):c.5020G>T (p.Gly1674Ter) (rs1407028917)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000761765	SCV000891955	likely pathogenic	not provided	2018-08-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000826211	SCV000967777	pathogenic	Rare genetic deafness	2019-07-16	criteria provided, single submitter	clinical testing	The p.Gly1674X variant in OTOG has been identified by our laboratory in one individual with mild hearing loss who carried a second pathogenic OTOG variant in trans, and both variants segregated with hearing loss in an affected sibling. The p.Gly1674X variant has also been reported by other clinical laboratories in ClinVar (Variation ID 623765) and has been identified in 0.02% (14/70668) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 1647, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOG gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting, PP1.