NM_194248.3(OTOF):c.2485C>T (p.Gln829Ter) AND Autosomal recessive nonsyndromic hearing loss 9

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 5, 2022
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:: RCV000006511.17

Allele description [Variation Report for NM_194248.3(OTOF):c.2485C>T (p.Gln829Ter)]

NM_194248.3(OTOF):c.2485C>T (p.Gln829Ter)

Gene:

OTOF:otoferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_194248.3(OTOF):c.2485C>T (p.Gln829Ter)

Other names:

NM_194248.3(OTOF):c.2485C>T

HGVS:

NC_000002.12:g.26477210G>A
NG_009937.1:g.86489C>T
NM_001287489.2:c.2485C>T
NM_004802.4:c.244C>T
NM_194248.3:c.2485C>TMANE SELECT
NM_194322.3:c.415C>T
NM_194323.3:c.244C>T
NP_001274418.1:p.Gln829Ter
NP_004793.2:p.Gln82Ter
NP_919224.1:p.Gln829Ter
NP_919224.1:p.Gln829Ter
NP_919224.1:p.Gln829Ter
NP_919303.1:p.Gln139Ter
NP_919304.1:p.Gln82Ter
NC_000002.11:g.26700078G>A
NM_194248.1:c.2485C>T
NM_194248.2:c.2485C>T
NM_194248.3:c.2485C>T
c.2485C>T
p.Gln829X

Protein change:

Q139*; GLN829TER

Links:

OMIM: 603681.0004; dbSNP: rs80356593

NCBI 1000 Genomes Browser:

rs80356593

Molecular consequence:

NM_001287489.2:c.2485C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004802.4:c.244C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_194248.3:c.2485C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_194322.3:c.415C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_194323.3:c.244C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Accession: GDS4123

GEO DataSets
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026694	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2006)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 12114484, 16371502
SCV000041704	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 12114484, 14635104
SCV003835879	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 5, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000026694

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2006)

germline

literature only

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

SCV000041704

GeneReviews

no classification provided

not provided

germline

literature only

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

SCV003835879

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 5, 2022)

unknown

clinical testing

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

Citations

PubMed

OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.

Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ.

J Med Genet. 2006 Jul;43(7):576-81. Epub 2005 Dec 21.

PubMed [citation]

PMID:: 16371502
PMCID:: PMC2593030

Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.

Migliosi V, Modamio-Høybjør S, Moreno-Pelayo MA, Rodríguez-Ballesteros M, Villamar M, Tellería D, Menéndez I, Moreno F, Del Castillo I.

J Med Genet. 2002 Jul;39(7):502-6. No abstract available.

PubMed [citation]

PMID:: 12114484
PMCID:: PMC1735186

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000026694.2

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

Description

Among 28 unrelated Spanish families with nonsyndromic sensorineural hearing loss (601071), Migliosi et al. (2002) identified 1 family with a mutation in the OTOF gene: a 2485C-T transition in exon 22, resulting in a premature stop codon, gln829 to ter (Q829X). Both parents were carriers of the mutation and their 2 affected children were homozygous. The mutation was not present in 200 unrelated Spanish controls with normal hearing. Genetic analysis of another 269 unrelated patients with hearing loss revealed 11 more cases (8 sporadic and 3 familial) of the Q829X mutation. One of these families was compound heterozygous for Q829X and P1825A (603681.0005). Migliosi et al. (2002) determined that the Q829X mutation was responsible for 4.4% of recessive familial or sporadic cases of deafness in the Spanish population, and presented evidence for a founder effect.

Varga et al. (2006) found the Q829X mutation in 2 families. They referred to Q829X as the Hispanic mutation, it having been found in a group of Spanish families and 1 Cuban family as noted. They described it in a family from England with no known Hispanic ancestry. In a family of Mexican ancestry, the Q829X mutation was present in heterozygous state.

#	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 GeneReviews, SCV000041704.2

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

#	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 Baylor Genetics, SCV003835879.1

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

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

Last Updated: May 26, 2024

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