Submissions for variant NM_194248.3(OTOF):c.3966C>G (p.Asp1322Glu)

gnomAD frequency: 0.00096  dbSNP: rs80356576

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041537	SCV000065232	uncertain significance	not specified	2018-08-10	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Asp1322Glu va riant in OTOF has been previously reported by our laboratory in 3 heterozygous C aucasian and 1 heterozygous Latino individuals with hearing loss, but none had a second OTOF variant. The p.Asp1322Glu variant has also been reported as a benig n variant based on its identification in both cases and controls (Varga 2006). I t has also been reported in ClinVar (Variation ID 21848) and has been identified in 0.1% (170/126566) of European chromosomes by gnomAD (http://gnomad.broadinst itute.org; dbSNP rs80356576). Computational prediction tools and conservation an alysis suggest that the p.Asp1322Glu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, wh ile the clinical significance of the p.Asp1322Glu variant is uncertain, these da ta suggest that it is more likely to be benign. ACMG/AMP Criteria applied: PP3, BS1_Supporting.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514025	SCV000610350	likely benign	not provided	2017-06-26	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000514025	SCV001144823	uncertain significance	not provided	2019-03-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514025	SCV001246605	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000021060	SCV001302003	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV000514025	SCV001796266	uncertain significance	not provided	2021-03-26	criteria provided, single submitter	clinical testing	Observed in one or more patients with hearing loss in published literature; no specific information provided (Varga et al., 2006); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16371502)
Invitae	RCV000514025	SCV002109073	likely benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000021060	SCV003816536	uncertain significance	Autosomal recessive nonsyndromic hearing loss 9	2019-01-18	criteria provided, single submitter	clinical testing
GeneReviews	RCV000021060	SCV000041715	not provided	Autosomal recessive nonsyndromic hearing loss 9		no assertion provided	literature only