Identifying the causative variant from among the thousands identified by whole exome sequencing (WES) or whole genome sequencing (WGS) 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 (http://researchphenodb.net and http://phenodb.org). 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 (http://genematcher.org), a freely accessible web site that enables connections between clinicians and researchers across the world who share an interest in the same gene(s). This article is protected by copyright. All rights reserved.