Submissions for variant NM_001292063.2(OTOG):c.7534C>T (p.Arg2512Cys)

gnomAD frequency: 0.00056  dbSNP: rs533820347

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522896	SCV000619238	uncertain significance	not specified	2017-07-26	criteria provided, single submitter	clinical testing	The R2524C variant in the OTOG gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Reliable data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, the R2524C variant is observed in 73/76,088 (0.1%) alleles from individuals undergoing testing at GeneDx, and no individuals are reported to be homozygous. The R2524C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R2524C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002060271	SCV002336414	benign	not provided	2024-01-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003962448	SCV004782947	benign	OTOG-related disorder	2024-09-26	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).