MYO1A G662E - GET-Evidence

Curation:
Currentness:

MYO1A G662E

(MYO1A Gly662Glu)


Short summary

Although one report speculated that this variant may cause dominant, early-onset sensorineural hearing loss, the findings lacked statistical significance. Notably, this gene is not a clinically tested gene and another of the eight variants reported by these authors (S797F) has since been observed in a PGP participant with no symptoms of hearing loss.

Variant evidence
Computational

Polyphen 2 predicts benign effect, but BLOSUM100 score indicates Gly to Glu is often disruptive.

Functional -
Case/Control

No statistically significant findings.

See Donaudy F et al. 2003 (12736868).

Familial -
 
Clinical importance
Severity 3

Mild deafness.

Treatability 1
Penetrance 5

Published hypothesis is a dominant effect.

 

Impact

Moderate clinical importance, Uncertain pathogenic

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

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr12:57431402: 2.6% (277/10758) in EVS
  • Frequency shown in summary reports: 2.6% (277/10758)

Publications
 

Donaudy F, Ferrara A, Esposito L, Hertzano R, Ben-David O, Bell RE, Melchionda S, Zelante L, Avraham KB, Gasparini P. Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss. Am J Hum Genet. 2003 Jun;72(6):1571-7. Epub 2003 May 6. PubMed PMID: 12736868; PubMed Central PMCID: PMC1180318.

In a screen of the MYO1A gene in 230 Italian patients with sensorineural hearing loss who were negative for mutations in GJB2. This variant was found in a 5-year-old male patient with mild hearing loss, and was not found in 200 population matched control chromosomes (we assume this represents 100 control individuals). The authors note this position is not evolutionarily conserved and state that follow-up observations will be needed to determine whether the variant is pathogenic. Counting carriers this is case+: 1, case-: 229, control+: 0, control-: 100.

Notably, this paper is investigating the new hypothesis that variants in this gene may cause hearing loss. The authors list 8 total variants impacting protein structure found in a screen of 230 unrelated patients (one nonsense, one in-frame trinucleotide insertion, and 6 missense) and state that these variants were not seen in 200 control chromosomes (which we treat as 100 control individuals). Notably, they do not mention how many other variants impacting protein structure (nonsynonymous substitutions, etc) were found in the controls (this would be the appropriate test). Even if there were none, these numbers for gene data taken as a whole (case+: 8, case-:222, control+: 0, control-:100) do not appear to be significant: two-tailed Fisher’s exact test gives a p-value = 0.112. Another of the 8 variants reported by these authors (S797F) has been observed in a healthy PGP participant with no hearing loss.

Genomes
 

Other external references
 

    dbSNP
  • rs33962952
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.001 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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