NM_001292063.1(OTOG):c.499del (p.Val167fs) AND Rare genetic deafness

Clinical significance:Likely pathogenic (Last evaluated: Feb 4, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000218007.1

Allele description [Variation Report for NM_001292063.1(OTOG):c.499del (p.Val167fs)]

NM_001292063.1(OTOG):c.499del (p.Val167fs)

Gene:
OTOG:otogelin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p15.1
Genomic location:
Preferred name:
NM_001292063.1(OTOG):c.499del (p.Val167fs)
HGVS:
  • NC_000011.10:g.17553478del
  • NG_033191.1:g.11106del
  • NG_033191.2:g.11106del
  • NM_001292063.1:c.499del
  • NP_001278992.1:p.Val167fs
  • NC_000011.9:g.17575025del
  • NC_000011.9:g.17575025delG
  • NM_001277269.1:c.535delG
  • p.Val179TrpfsX53
Protein change:
V167fs
Links:
dbSNP: rs876657657
NCBI 1000 Genomes Browser:
rs876657657
Molecular consequence:
  • NM_001292063.1:c.499del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: CN826980; Orphanet: 96210

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000271254Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Feb 4, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not 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, Partners HealthCare Personalized Medicine, SCV000271254.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Val179fs variant in OTOG has not been previously reported in individuals w ith hearing loss. This variant has been identified in 1/722 of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org); h owever, this frequency is low enough to be consistent with a recessive carrier f requency. This variant is predicted to cause a frameshift, which alters the prot ein?s amino acid sequence beginning at position 179 and leads to a premature ter mination codon 53 amino acids downstream. This alteration is then predicted to l ead to a truncated or absent protein. Two loss of function variants in the OTOG gene have been reported to segregate with hearing loss in two families (Schrader s 2012), and disruption of Otog in mice resulted in deafness supporting of a los s-of-function mechanism for the disease (Simmler 2000). While these two studies provide evidence of a causative link between loss of function of OTOG and autoso mal recessive hearing loss, to date, no other publications report on OTOG varian ts in individuals with hearing loss. In summary, although additional evidence is required to strengthen the gene-disease association for OTOG and hearing loss, the current data supports a likely pathogenic role for the p.Val179fs variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Sep 29, 2021

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