Variant Nomination Data


Reasons for Acceptance


The following is a list of reasons nominated variants were accepted for modeling by the center:

  • Generation of a preclinical model for planned therapy studies (e.g., gene therapy, ASO, nutritional intervention)
  • Modeling of variants in mouse for phenotypic studies that will provide evidence for a novel disease gene in pediatric or adult populations
  • Modeling of variants in fly for studies of the functional impact of variant on protein function to provide evidence of a novel disease gene in pediatric or adult populations
  • Modeling of a variant in a known disease gene in the mouse to provide evidence of phenotypic expansion 

Reasons for Rejection


The following list contains examples of reasons why variants were not selected for modeling by the center:

  • Inability to faithfully model variant due to technical limitations
  • Variant of uncertain significance in a known disease gene where phenotype is consistent with known disease phenotype, and there were no other plans for studying the model once phenotyping was completed
  • Variant involved a poorly conserved residue and bioinformatic tools did not provide strong evidence of pathogenicity
  • Identification of a similar variant in the literature upon review by the Center, and model was no longer deemed necessary by nominator
  • Multiple matches in GeneMatcher or other databases such that the model was no longer deemed necessary by nominators
  • Identification of a suitable research project with the ability to provide a quicker answer with regards to whether the variant impacts protein function
  • Homozygous common variant in a gene where knockout mouse has previously been generated, and mouse phenotype was not similar to human phenotype 
  • Low percentage of phenotypic mice observed in established mouse models of other variants in the same gene

In many cases, the Center refers variants deemed unsuitable for modeling in the center to other research projects that may be more appropriate for answering the question(s) posed by the nominator.