Submissions for variant NM_194248.3(OTOF):c.4091G>T (p.Gly1364Val)

gnomAD frequency: 0.00155  dbSNP: rs138037294

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Hearing Loss Variant Curation Expert Panel	RCV002235592	SCV002512130	likely benign	Nonsyndromic genetic hearing loss	2022-05-13	reviewed by expert panel	curation	The filtering allele frequency (the lower threshold of the 95% CI of 128/24484) of the c.4091G>T (p.Gly1364Val) variant in the OTOF gene is 0.449% for African/African-American chromosomes by gnomAD, which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825800	SCV000967269	likely benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Gly1364Val in Exon 34 of OTOF: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (16/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs138037294).
Invitae	RCV000921292	SCV001066692	likely benign	not provided	2024-01-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000921292	SCV001778899	likely benign	not provided	2021-05-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002536063	SCV003712505	uncertain significance	Inborn genetic diseases	2021-12-03	criteria provided, single submitter	clinical testing	The c.4091G>T (p.G1364V) alteration is located in exon 34 (coding exon 34) of the OTOF gene. This alteration results from a G to T substitution at nucleotide position 4091, causing the glycine (G) at amino acid position 1364 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003955538	SCV004771351	likely benign	OTOF-related condition	2019-11-26	criteria provided, single submitter	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).