What is the HEAR VUS Program?
- Comprehensive genetic testing is fast and accurate but understanding the impact of Variants of Uncertain Significance (VUS) is not always straightforward. The HEAR VUS program offers follow up testing at no additional cost for family members of a patient previously tested with OtoSCOPE®.
The HEAR VUS program aims to:
Provide the most clinically relevant information about variants identified in families.
Improve knowledge about genetic variants for the medical and scientific communities.
Evaluate the pathogenicity of a variant when its contribution is uncertain and cannot be determined as pathogenic or benign.
Quick Facts
- Test Code: HEARVUS
- Turnaround Time: 6 weeks
Request an evaluation:
To be evaluated if you or your patient will qualify, use this form.
Shipping Requirements
(SEND ONLY ONE OF THE FOLLOWING SAMPLE TYPES) :
- 5µg DNA suspended in ≥ 50µl elution buffer
- minimum concentration 50ng/µl
- A260/A280 1.8-2.0
- 3-5 cc EDTA Whole Blood
- room temperature
- Saliva
- DNA Genotek, ORAGene Discover, OGR-500
- Buccal Swabs
- at least 4 swabs
- DNA Genotek, OraCollect, OCD-100
- Whole Blood Sample Stability for DNA extraction
- EDTA Whole Blood is stable for 7 days at room temperature and 4 months in the refrigerator
- Saliva Collection Kits and Buccal Swabs Sample Stability
- Per the manufacturer for samples collected following the instructions provided with kit/swabs: OGR-500 saliva collection kits are stable at room temperature for several years and OCD-100 buccal swabs stable up to 80 days. Both of these kits can be shipped at room temperature.
- Labeled with the sample type AND patient’s name, DOB, MRN and sex
- Room temperature (DO NOT FREEZE)
- Samples may be refrigerated if delivery is delayed
- Shipping and receiving dock closed on weekends and holidays
- Deliveries accepted Monday - Friday
Provide a pedigree, audiograms, clinic notes regarding hearing loss and temporal bone imaging studies (if performed).
Helping Evaluate And Reclassify Variants of Unknown Significance (HEAR VUS)
The HEAR VUS program incorporates evaluation of a VUS in the context of a patient’s and family’s clinical information by testing additional family members and reviewing the most up-to-date information available for the VUS under consideration.
The VUS is evaluated by the MORL Hearing Team, which includes physicians, genetic counselors, bioinformaticians, graduate students, post-doctoral fellows, medical students, medical residents, and scientists.
The VUS is discussed in the context of available clinical information.
There are two ways to participate in the HEAR VUS program:
Complimentary testing may be offered by the MORL in the body of OtoSCOPE reports.
Healthcare providers may request complimentary testing through the HEAR VUS program by submitting an evaluation request form, including relevant clinical information like family history and audiometric information.
Following a HEAR VUS offer or accepted evaluation request, a Hearing Testing requisition and a sample must be submitted to MORL.
After testing, a report will be sent to the ordering healthcare provider.
If the VUS is reclassified following further evaluation, MORL will issue an amended report for the proband and tested family members.
Complimentary testing will not be offered to family members if:
The variant has been classified previously as pathogenic, likely pathogenic, likely benign or benign.
The VUS is in a gene that is not consistent with the patient’s reported clinical history (for example: age of onset, degree of hearing loss, reported family history).
The variant is associated with an inheritance pattern such that further familial testing will not clarify the significance of the variant.
The VUS is associated with autosomal recessive hearing loss and a second variant is not present in that gene.
The VUS has a minor allele frequency greater than expected to cause hearing loss.
The relevant clinical information is not made available. In this situation, Fee-for-Service Familial Testing may be ordered.
Please note, incidental and secondary findings are not evaluated through this program.
Variant interpretation is complex and relies on all available clinical, phenotypic, and genetic information. There is no single method, tool, or filter that reliably determines pathogenicity, so expert analysis is required.
Variants are discussed at the MORL Hearing Group meeting to integrate the available clinical information with results from OtoSCOPE and the HEAR VUS program to determine a most likely genetic cause of deafness, if any.
Each variant is interpreted utilizing ACMG guidelines to determine pathogenicity.
Using all available information and ACMG guidelines, our Hearing Group will exclude non-causative variants from consideration.
Possible justifications for exclusion of a variant may include, but are not limited to the following reasons:
Causality of the identified variant is not consistent with the reported family history.
Causality of the identified variant is not consistent with the clinical description and/or phenotypic information provided to MORL.
Causality of the identified variant is unlikely based on pathogenicity prediction scores.
Allele frequency is too high.
Do you have questions about the HEAR VUS Program? Contact MORL Hearing Team at MORL@uiowa.edu and add “HEAR VUS” in the email subject line.
The Clinical Diagnostics Service of the Molecular Otolaryngology & Renal Research Laboratories is a CLIA-approved, Joint Commission-accredited diagnostic laboratory.