NM_194248.3(OTOF):c.5375G>A (p.Arg1792His) AND Autosomal recessive nonsyndromic hearing loss 9

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 17, 2024
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:: RCV000656336.5

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:: Autosomal recessive nonsyndromic hearing loss 9
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 9; Deafness, autosomal recessive 9; AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1, TEMPERATURE-SENSITIVE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010986; MedGen: C1832828; Orphanet: 90636; OMIM: 601071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000778299	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Likely pathogenic (Feb 13, 2018)	germline	clinical testing
SCV000804276	OMIM	no assertion criteria provided	Pathogenic (Aug 31, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004804932	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000778299

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

no assertion criteria provided

Likely pathogenic
(Feb 13, 2018)

germline

clinical testing

SCV000804276

OMIM

no assertion criteria provided

Pathogenic
(Aug 31, 2018)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004804932

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 17, 2024)

germline

research

PubMed (1)
[See all records that cite this PMID]

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	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV000778299.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From OMIM, SCV000804276.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In affected members from 4 (F-18, F-22, F-31, and F-32) of 33 Saudi families with autosomal recessive prelingual sensorineural hearing loss (DFNB9; 601071), Almontashiri et al. (2018) identified homozygosity for a c.5375G-A transition in the OTOF gene that resulted in an arg1792-to-his (R1792H) amino acid substitution. Almontashiri et al. (2018) observed this variant in 1 of 252,426 alleles from non-Middle Eastern populations in the gnomAD database.

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

From Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre, SCV004804932.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	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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