NM_019098.4(CNGB3):c.1148delC (p.Thr383Ilefs)

NM_019098.4(CNGB3):c.1148delC (p.Thr383Ilefs)

Variant type:
Deletion
Cytogenetic location:
8q21-q22
Genomic location:
  • Chr8:87656009 (on Assembly GRCh37)
  • Chr8:86643781 (on Assembly GRCh38)
HGVS:
  • NG_016980.1:g.104895delC
  • NM_019098.4:c.1148delC
  • NC_000008.11:g.86643781delG
  • NC_000008.10:g.87656009delG
  • NP_061971.3:p.Thr383Ilefs
  • NM_019098.3:c.1148delC
Links:
NCBI 1000 Genomes Browser:
rs397515360
Molecular consequence:
NM_019098.4:c.1148delC: frameshift variant [Sequence Ontology SO:0001589]

Clinical significance

NM_019098.4(CNGB3):c.1148delC (p.Thr383Ilefs)

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
(2/4)2 stars out of maximum of 4 stars
classified by multiple submitters
Number of submission(s):
4
Condition(s)
See supporting ClinVar records

Recent Activity

Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(Sep 8, 2011)
classified by single submitter
(literature only)
literature onlygermlinePubMed (5)
OMIM
(Dec 30, 2010)
SCV000025717
Pathogenic
(Sep 8, 2011)
classified by single submitter
(literature only)
literature onlygermlinePubMed (5)
OMIM
(Dec 30, 2010)
SCV000025718
Pathogenic
(Jun 27, 2013)
classified by single submitter
(literature only)
literature onlynot providedPubMed (2)
GeneReviews
(Apr 30, 2013)
SCV000086982
Pathogenic
(Aug 5, 2013)
classified by single submitter
(clinical testing)
clinical testing
  • not provided
germlinePubMed (4)
Citation Link
Emory Genetics Laboratory
(Nov 21, 2013)
SCV000113913

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermline, not providednot providednot provided

Emory Genetics Laboratory

Observations

FamiliesIndividualsSegregationAllele originObserved phenotypesEthnicityGeographic originCollection methodDescription
not providednot providednot providedgermlinenot providednot providednot providedclinical testing
(GTR000503140)
See description

GeneReviews

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providednot provided

Description

not provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

In a female patient with achromatopsia and systemic features associated with maternal uniparental disomy for chromosome 14, previously reported by Pentao et al. (1992), and in 7 other unrelated patients with achromatopsia, Wiszniewski et al. (2007) identified homozygosity for the 1148delC mutation. Two other patients were found to be compound heterozygotes for the 1148delC mutation and another CNGB3 mutation. Analysis of intragenic SNPs revealed transmission of a common haplotype consistent with a founder effect.
In an 8-year-old girl with a diagnosis of juvenile macular degeneration (see 248200), Nishiguchi et al. (2005) identified a 1405T-G transversion in the CNGB3 gene (605080.0006), resulting in a tyr469-to-asp substitution. The girl also carried the 1148delC mutation (T383fs), but since segregation analysis could not be performed, compound heterozygosity was presumed. She had no family history of retinal disease and no visual complaints.
In the course of screening the CNGB3 gene in patients with achromatopsia (262300) from 15 Pingelapese families, Sundin et al. (2000) found 2 brothers, aged 18 and 15 years, with total colorblindness, photophobia, nystagmus, 20/200 visual acuity, and a normal-appearing retina. Electroretinography of the older brother revealed a normal rod response and no cone response. Both brothers were healthy and of normal intelligence. One allele in the brothers carried an 8-bp deletion in exon C and the other allele carried a 1-bp deletion in exon G. Each deletion caused a frameshift in the CNGB3 coding region that eliminated all downstream protein sequence, including the critical pore, S6 transmembrane, and cGMP-binding domains. The 8-bp deletion was inherited from the father and the 1-bp deletion (T383fs) from the mother. The 1-bp deletion was found in heterozygous state in a 12-month-old girl who exhibited horizontal nystagmus, marked photophobia, a normal electroretinographic rod response, and no detectable cone response. Thus, these deletion mutations provided independent confirmation of the identity of the gene and its role in complete achromatopsia. Kohl et al. (2000) identified the 1-bp deletion in ACHM patients of different geographic origin.

Last Updated: Aug 5, 2014

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