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NM_001292063.2(OTOG):c.379C>T (p.Gln127Ter) AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 23, 2019
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:
RCV001195541.4

Allele description [Variation Report for NM_001292063.2(OTOG):c.379C>T (p.Gln127Ter)]

NM_001292063.2(OTOG):c.379C>T (p.Gln127Ter)

Gene:
OTOG:otogelin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.1
Genomic location:
Preferred name:
NM_001292063.2(OTOG):c.379C>T (p.Gln127Ter)
HGVS:
  • NC_000011.10:g.17553205C>T
  • NG_033191.2:g.10833C>T
  • NM_001277269.2:c.415C>T
  • NM_001292063.2:c.379C>TMANE SELECT
  • NP_001264198.1:p.Gln139Ter
  • NP_001278992.1:p.Gln127Ter
  • NC_000011.9:g.17574752C>T
  • NG_033191.1:g.10833C>T
Protein change:
Q127*
Links:
dbSNP: rs1851981434
NCBI 1000 Genomes Browser:
rs1851981434
Molecular consequence:
  • NM_001277269.2:c.415C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001292063.2:c.379C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001365922Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Dec 23, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown21not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001365922.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

The p.Gln139X variant in OTOG has been reported by our laboratory in 1 individual with hearing loss who harbored the c.2116+5G>C variant of uncertain significance in trans. The p.Gln139X variant is absent from large population studies. This nonsense variant leads to a premature termination codon at position 139, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOG gene is an established disease mechanism in autosomal recessive hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM2, PM3_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not provided1not provided

Last Updated: Dec 24, 2023