New tools for Mendelian disease gene identification: PhenoDB variant analysis module; and GeneMatcher, a web-based tool for linking investigators with an interest in the same gene

Hum Mutat. 2015 Apr;36(4):425-31. doi: 10.1002/humu.22769.


Identifying the causative variant from among the thousands identified by whole-exome sequencing or whole-genome sequencing is a formidable challenge. To make this process as efficient and flexible as possible, we have developed a Variant Analysis Module coupled to our previously described Web-based phenotype intake tool, PhenoDB ( and When a small number of candidate-causative variants have been identified in a study of a particular patient or family, a second, more difficult challenge becomes proof of causality for any given variant. One approach to this problem is to find other cases with a similar phenotype and mutations in the same candidate gene. Alternatively, it may be possible to develop biological evidence for causality, an approach that is assisted by making connections to basic scientists studying the gene of interest, often in the setting of a model organism. Both of these strategies benefit from an open access, online site where individual clinicians and investigators could post genes of interest. To this end, we developed GeneMatcher (, a freely accessible Website that enables connections between clinicians and researchers across the world who share an interest in the same gene(s).

Keywords: Mendelian disease; mutation; next-generation sequencing; whole-exome sequencing; whole-genome sequencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Computational Biology / methods*
  • Databases, Genetic*
  • Genetic Association Studies / methods*
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics*
  • Genetic Variation
  • Genomics / methods*
  • Internet
  • Phenotype
  • Software*
  • Web Browser