Submissions for variant NM_001292063.2(OTOG):c.8125G>A (p.Asp2709Asn)

gnomAD frequency: 0.00084  dbSNP: rs189910531

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000602323	SCV000711619	uncertain significance	not specified	2017-01-10	criteria provided, single submitter	clinical testing	The p.Asp2721Asn variant in OTOG has not been previously reported in individuals with hearing loss, but has been identified in 1/868 of African chromosomes and 1/272 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs189910531). Although this variant has been seen in t he general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis do not provide s trong support for or against an impact to the protein. In summary, the clinical significance of the p.Asp2721Asn variant is uncertain.
Baylor Genetics	RCV001333074	SCV001525559	uncertain significance	Autosomal recessive nonsyndromic hearing loss 18B	2019-12-26	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001591362	SCV001825789	uncertain significance	not provided	2024-08-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001591362	SCV002171438	uncertain significance	not provided	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 2721 of the OTOG protein (p.Asp2721Asn). This variant is present in population databases (rs189910531, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with OTOG-related conditions. ClinVar contains an entry for this variant (Variation ID: 504840). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV001333074	SCV003816544	uncertain significance	Autosomal recessive nonsyndromic hearing loss 18B	2019-03-24	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001591362	SCV001958487	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001591362	SCV001975293	uncertain significance	not provided		no assertion criteria provided	clinical testing