NM_194248.3(OTOF):c.5375G>A (p.Arg1792His) AND Nonsyndromic genetic hearing loss

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 5, 2025
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV005237462.1

Allele description [Variation Report for NM_194248.3(OTOF):c.5375G>A (p.Arg1792His)]

NM_194248.3(OTOF):c.5375G>A (p.Arg1792His)

Gene:

OTOF:otoferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_194248.3(OTOF):c.5375G>A (p.Arg1792His)

HGVS:

NC_000002.12:g.26461854C>T
NG_009937.1:g.101845G>A
NM_001287489.2:c.5375G>A
NM_004802.4:c.3074G>A
NM_194248.3:c.5375G>AMANE SELECT
NM_194322.3:c.3305G>A
NM_194323.3:c.3074G>A
NP_001274418.1:p.Arg1792His
NP_004793.2:p.Arg1025His
NP_919224.1:p.Arg1792His
NP_919303.1:p.Arg1102His
NP_919304.1:p.Arg1025His
NC_000002.11:g.26684722C>T
NM_001287489.1:c.5375G>A
NM_004802.3:c.3074G>A
NM_194248.2:c.5375G>A
NM_194248.3:c.5375G>A
c.5375G>A

Protein change:

R1025H; ARG1792HIS

Links:

OMIM: 603681.0015; dbSNP: rs111033349

Molecular consequence:

NM_001287489.2:c.5375G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004802.4:c.3074G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194248.3:c.5375G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194322.3:c.3305G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194323.3:c.3074G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Nonsyndromic genetic hearing loss
Synonyms:: Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:: MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005886368	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 5, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31095577, 29048421 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005886368

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 5, 2025)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients.

Iwasa YI, Nishio SY, Sugaya A, Kataoka Y, Kanda Y, Taniguchi M, Nagai K, Naito Y, Ikezono T, Horie R, Sakurai Y, Matsuoka R, Takeda H, Abe S, Kihara C, Ishino T, Morita SY, Iwasaki S, Takahashi M, Ito T, Arai Y, Usami SI.

PLoS One. 2019;14(5):e0215932. doi: 10.1371/journal.pone.0215932.

PubMed [citation]

PMID:: 31095577
PMCID:: PMC6522017

Recurrent variants in OTOF are significant contributors to prelingual nonsydromic hearing loss in Saudi patients.

Almontashiri NAM, Alswaid A, Oza A, Al-Mazrou KA, Elrehim O, Tayoun AA, Rehm HL, Amr SS.

Genet Med. 2018 Apr;20(5):536-544. doi: 10.1038/gim.2017.143. Epub 2017 Oct 19.

PubMed [citation]

PMID:: 29048421
PMCID:: PMC5929117

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005886368.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: OTOF c.5375G>A (p.Arg1792His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251482 control chromosomes. c.5375G>A has been reported in the literature in multiple homozygous or compound heterozygous individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 9 (e.g. Almontashiri_2018, Iwasa_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29048421, 31095577). ClinVar contains an entry for this variant (Variation ID: 48259). Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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