USH1C V130I - GET-Evidence

Curation:
Currentness:

USH1C V130I

(USH1C Val130Ile)


Short summary

This moderately common variant (1000 genomes allele frequency of 6.2%) was reported found heterozygously in a patient with Usher syndrome. However, the high allele frequency and fact that it is a conservative amino acid change supports classifying this variant as benign.

Variant evidence
Computational 2

Conservative amino acid change and polyphen 2 predict benign effect.

Functional -
Case/Control 1

High allele frequency in 1000 genomes supports no strong pathogenic effect.

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr11:17548878: 1.7% (179/10758) in EVS
  • T @ chr11:17505453: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 1.7% (179/10758)

Publications
 

Blaydon DC, Mueller RF, Hutchin TP, Leroy BP, Bhattacharya SS, Bird AC, Malcolm S, Bitner-Glindzicz M. The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK. Clin Genet. 2003 Apr;63(4):303-7. PubMed PMID: 12702164.

In a screen of 30 patients and families with Usher syndrome type 1, this variant was seen heterozygously in one patient and not seen in 96 normal control individuals. Authors are unsure whether this variant is pathogenic, they note that it may be a rare polymorphism as it is a conservative amino acid change and isn’t predicted to affect splicing.

Genomes
 

GS19129 - var-GS19129-1100-36-ASM
het T @ chr11:17505454

 

GS19703 - var-GS19703-1100-36-ASM
het T @ chr11:17505454

 

Other external references
 

    dbSNP
  • rs55843567
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the USH1C gene
    DFNB18 Nonsyndromic Hearing Loss and Deafness
    Nonsyndromic Hearing Loss and Deafness, Autosomal Recessive
    Usher Syndrome Type 1
    Usher Syndrome Type 1C
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/USH1C
    Web search results (5 hits -- see all)
  • OMIM: 605242
    The inner ear Ush1c transcripts predicted several harmonin isoforms, some containing an additional coiled ... 5 of the USH1C gene, resulting in a val130-to-ile (V130I) mutation. ...
    www.genome.jp/dbget-bin/www_bget?omim+605242

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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