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NM_194248.3(OTOF):c.4275G>A (p.Trp1425Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 25, 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:
RCV003556064.2

Allele description [Variation Report for NM_194248.3(OTOF):c.4275G>A (p.Trp1425Ter)]

NM_194248.3(OTOF):c.4275G>A (p.Trp1425Ter)

Gene:
OTOF:otoferlin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_194248.3(OTOF):c.4275G>A (p.Trp1425Ter)
HGVS:
  • NC_000002.12:g.26467186C>T
  • NG_009937.1:g.96513G>A
  • NM_001287489.2:c.4275G>A
  • NM_004802.4:c.1974G>A
  • NM_194248.3:c.4275G>AMANE SELECT
  • NM_194322.3:c.2205G>A
  • NM_194323.3:c.1974G>A
  • NP_001274418.1:p.Trp1425Ter
  • NP_004793.2:p.Trp658Ter
  • NP_919224.1:p.Trp1425Ter
  • NP_919303.1:p.Trp735Ter
  • NP_919304.1:p.Trp658Ter
  • NC_000002.11:g.26690054C>T
  • NM_194248.1:c.4275G>A
Protein change:
W1425*
Links:
dbSNP: rs80356598
NCBI 1000 Genomes Browser:
rs80356598
Molecular consequence:
  • NM_001287489.2:c.4275G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004802.4:c.1974G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_194248.3:c.4275G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_194322.3:c.2205G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_194323.3:c.1974G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004292081Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 25, 2024) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292081.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Trp1425*) 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 present in population databases (rs80356598, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with non-syndromic hearing loss (PMID: 33297549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 21849). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024