RNA to the RESCUE: Evaluation to Assess the Clinical Utility of RNA Sequencing in Establishing a Genetic Diagnosis or Adjudicating a Previously Established Genetic Diagnosis.

RNAseq for the Evaluation of Splicing and Cryptic or Unrecognized Effects

The goal of this observational study is to see if ribonucleic acid (RNA) sequencing can improve the diagnostic yield and accuracy of genetic testing compared to gene sequencing alone. Participants will be asked to share their medical history and prior genetic testing results, and to donate a blood sample for testing.

Participant will come on site for a one-time blood draw. Study personnel will review prior medical history, family history, and prior genetic testing results gathered from the participant's medical record, along with analysis of RNA sequencing results derived from participant's blood sample. Results will be shared with participants through their clinical geneticist.

Inclusion Criteria:

• individuals who have previously undergone gene panel testing, WES or WGS with no diagnostic findings but with high suspicion for a genetic etiology
• individuals who have undergone genetic testing and who are found to have a truncating variant classified as pathogenic in a disease-causing gene but lack many/all symptoms typically associated with the disorder.

Exclusion Criteria:

• none