Rapid Mendelian Genes Sequencing Panel, Trio

Mendelian diseases are inherited conditions linked to individual genes. This test entails rapid sequencing of ~4,900 genes of known function from a critically ill individual and both parents to quickly diagnose a Mendelian disease to improve medical management. 

Test Overview

• Although humans have ~19,000 genes, the function of only ~4,900 genes is known.
  • This test only sequences genes with known function
• See Rapid Mendelian Sequencing Gene List for genes included in this panel.
• Parental specimens are required to identify de novo variants and to determine phase and clinical significance of variants detected in proband.

• Blood specimens from the proband and both parents
• Completed Informed Consent for Rapid Mendelian Genes Sequencing Panel, Trio form for proband
• Completed Patient History for Rapid Mendelian Genes Sequencing Panel, Trio form
• Clinical summary from genetic consultation (if available)
• Three-generation medical pedigree
• Copy of abnormal results, which may include:
  • Genomic microarray
  • Skeletal survey
  • Magnetic resonance imaging (MRI)

Clinical Sensitivity

50% for infants  

Reporting and Interpretation

• Accurate representation of biological relationships between family members is imperative for correct test interpretation.
• Only variants predicted to be related to the patient’s medical issues are reported.
• Interpretation is based on information available at the time of testing and may change in the future.

Secondary Findings

• American College of Medical Genetics and Genomics (ACMG) recommends that disease-causing variants in specific genes (see ACMG list in table below) be reported whether or not they are related to the patient’s medical issues. 
  • This information may enable disease monitoring or early treatment.
  • Single pathogenic variants in autosomal recessive genes from this list are not reported.
• Additional medically actionable secondary findings may be reported at ARUP’s discretion.
• Pathogenic variants in genes recommended by ACMG, or other medically actionable secondary findings in non-ACMG genes, are reported if elected on the consent form.
• Parental inheritance is not reported for secondary variants detected in the proband.
• Parents are not issued reports of secondary findings.
• Familial Mutation, Targeted Sequencing (2001961) can be ordered on the parents to test for a medically actionable secondary finding reported in the proband.

Limitations

• A negative result does not exclude the possibility of a genetic condition.
• Diagnostic errors can occur due to rare sequence variations.
• Interpretation of this test result may be impacted if the individual or his/her parents have had an allogeneic stem cell transplantation.
• The following will not be evaluated:
  • Genes with unknown function
  • Variants outside coding regions and intron-exon boundaries of the targeted genes
  • Regulatory region variants and deep intronic variants
  • Large deletions/duplications
  • Noncoding transcripts
• The following may not be detected:
  • Deletions/duplications/insertions of any size by massively parallel sequencing
  • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
  • Pathogenic ACMG variants that cannot be detected by massively parallel sequencing
  • Low-level mosaic variants

Analytic Sensitivity