Submissions for variant NM_194248.3(OTOF):c.5063C>T (p.Thr1688Met)

gnomAD frequency: 0.00133  dbSNP: rs111033393

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041560	SCV000065255	likely benign	not specified	2012-05-08	criteria provided, single submitter	clinical testing	Thr1688Met in exon 40 of OTOF: This variant has been identified in three individ uals by our laboratory, none of whom had second OTOF variants and one of whom ha d another cause of hearing loss. In addition, this variant has been identified i n 0.19% (16/8600) of European American chromosomes in a broad population by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; dbSNP rs11103 3393). In summary, these data suggest this variant is likely benign.
Eurofins Ntd Llc (ga)	RCV000041560	SCV000343185	likely benign	not specified	2016-07-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000973013	SCV001120746	likely benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
Mendelics	RCV000986603	SCV001135636	likely benign	Autosomal recessive nonsyndromic hearing loss 9	2019-05-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000973013	SCV001144826	likely benign	not provided	2019-03-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000986603	SCV001303879	uncertain significance	Autosomal recessive nonsyndromic hearing loss 9	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV000973013	SCV001874255	uncertain significance	not provided	2024-10-31	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 reported in association with hearing loss to our knowledge; This variant is associated with the following publications: (PMID: 19461658)
PreventionGenetics, part of Exact Sciences	RCV004751244	SCV005348156	likely benign	OTOF-related disorder	2024-03-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).