USH1C V130I - GET-Evidence



(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 -


Low clinical importance, Uncertain benign

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

Inheritance pattern


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)


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.


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


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


Other external references

  • rs55843567
  • 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
    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. ...

Other in silico analyses

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

Edit history

Gene search

"GENE" or "GENE A123C":

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