VAR-MD: A tool to analyze whole exome-genome variants in small human pedigrees with mendelian inheritance

Murat Sincan, Dimitre R. Simeonov, David Adams, Thomas C. Markello, Tyler M. Pierson, Camilo Toro, William A. Gahl, Cornelius F. Boerkoel

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The analysis of variants generated by exome sequencing (ES) of families with rare Mendelian diseases is a time-consuming, manual process that represents one barrier to applying the technology routinely. To address this issue, we have developed a software tool, VAR-MD (), for analyzing the DNA sequence variants produced by human ES. VAR-MD generates a ranked list of variants using predicted pathogenicity, Mendelian inheritance models, genotype quality, and population variant frequency data. VAR-MD was tested using two previously solved data sets and one unsolved data set. In the solved cases, the correct variant was listed at the top of VAR-MD's variant ranking. In the unsolved case, the correct variant was highly ranked, allowing for subsequent identification and validation. We conclude that VAR-MD has the potential to enhance mutation identification using family based, annotated next generation sequencing data. Moreover, we predict an incremental advancement in software performance as the reference databases, such as Single Nucleotide Polymorphism Database and Human Gene Mutation Database, continue to improve.

Original languageEnglish (US)
Pages (from-to)593-598
Number of pages6
JournalHuman mutation
Issue number4
StatePublished - Apr 2012
Externally publishedYes


  • Exome
  • Mendelian
  • Next generation sequencing
  • Variant filtering

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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