NM_194248.3(OTOF):c.1468_1469del (p.Pro490fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 2, 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:: RCV003552285.2

Allele description [Variation Report for NM_194248.3(OTOF):c.1468_1469del (p.Pro490fs)]

NM_194248.3(OTOF):c.1468_1469del (p.Pro490fs)

Gene:

OTOF:otoferlin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_194248.3(OTOF):c.1468_1469del (p.Pro490fs)

HGVS:

NC_000002.12:g.26482520_26482521del
NG_009937.1:g.81182_81183del
NG_094754.1:g.596_597del
NM_001287489.2:c.1468_1469del
NM_194248.3:c.1468_1469delMANE SELECT
NP_001274418.1:p.Pro490fs
NP_919224.1:p.Pro490fs
NC_000002.11:g.26705384_26705385del
NC_000002.11:g.26705388_26705389del

Protein change:

P490fs

Molecular consequence:

NM_001287489.2:c.1468_1469del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_194248.3:c.1468_1469del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004263221	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18381613, 19250381, 22575033, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004263221

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.

Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R, Arslan E, Medá C, Curet C, Völter C, Sainz-Quevedo M, Castorina P, Ambrosetti U, Berrettini S, Frei K, Tedín S, Smith J, Cruz Tapia M, Cavallé L, Gelvez N, Primignani P, Gómez-Rosas E, et al.

Hum Mutat. 2008 Jun;29(6):823-31. doi: 10.1002/humu.20708.

PubMed [citation]

PMID:: 18381613

Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.

Choi BY, Ahmed ZM, Riazuddin S, Bhinder MA, Shahzad M, Husnain T, Riazuddin S, Griffith AJ, Friedman TB.

Clin Genet. 2009 Mar;75(3):237-43. doi: 10.1111/j.1399-0004.2008.01128.x.

PubMed [citation]

PMID:: 19250381
PMCID:: PMC3461579

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004263221.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Pro490Thrfs*26) in the OTOF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOF are known to be pathogenic (PMID: 18381613, 19250381, 22575033). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. For these reasons, this variant has been 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: Sep 29, 2024

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