September 1, 2021

Initiative helps physicians interpret genetic test results

A new institutional initiative will offer a secure and easy way for physicians at Vanderbilt University Medical Center to ask for help interpreting genetic test results for their patients.

A new institutional initiative will offer a secure and easy way for physicians at Vanderbilt University Medical Center to ask for help interpreting genetic test results for their patients.

The Genetics E-consult initiative, which has completed an eight-month trial run and is ready for a rollout throughout VUMC, allows physicians who have ordered genetic testing to ask for help clarifying the often-complicated results, at no additional cost to the patient.

Rizwan Hamid, MD, PhD

“The diagnoses of many human diseases can be improved by DNA tests, the number of which continues to increase every year,” said Rizwan Hamid, MD, PhD, Dorothy O. Wells Professor of Pediatrics, director of Pediatric Medical Genetics and Genomic Medicine and director of the Vanderbilt Undiagnosed Diseases Program (VUDP).

“More and more physicians are ordering these tests; however, the results many times are not straightforward. Sometimes, the results show a mutation or rare variant in a particular gene, and that explains the disease, but often the results show a rare variant in a gene, and it’s not clear the way the report is written that it is causing disease,” he said. “These uncertain results can cause a lot of confusion among clinicians.

“Most physicians don’t get training on how to interpret these uncertain results,” Hamid said. “It’s not part of medical school and residency programs. It’s not part of fellowship training. You come out a brilliant doctor, but you don’t have that training to interpret uncertain genomic/molecular test results,” Hamid said. “Also, time is a factor. Our physicians may be seeing 20 patients a day, and they may not have time to spend looking at a report that may contain results on up to 4,000 different genes. We’re letting our physicians know there’s help available.”

Janet Talbert, MS, CGC

The Genetics E-consult can be ordered for both adult and pediatric patients via VUMC’s eStar electronic health record. When physicians order a genomic/molecular test, and receive the report from the lab in eStar, they can select whether they need help interpreting the results.

Janet Talbert, MS, CGC, and Jennifer Kennedy, MS, CGC, are certified genetic counselors in the Division of Medical Genetics and Genomics at VUMC, working with Hamid to interpret test results. Talbert joined VUMC in January from the Department of Medicine, Interstitial Lung Disease Program at National Jewish Health and InformedDNA.

“It’s like having a little genetic consult in a box that physicians can use,” Talbert said. “Some of the rare variants the lab may identify may be benign or they may be harmful. To interpret a report, a physician would have to search various databases and/or do literature searches. They may have to dig deeper and comb through medical records, draw out a family tree to look and see how these rare variants are being passed down through a family. It’s not always clear cut,” Talbert said. “Sometimes you need to call the testing laboratory to get clarification or request that other family members be tested,” she said, adding that if the testing of family members is requested by the genetics counselors, often there is no cost to the patient or family.

Jennifer Kennedy, MS, CGC

“Sometimes we can make recommendations for next best steps or direct the physician’s attention to subtle connections between the rare variant and the patient’s symptoms and signs, thus putting the physician in a much better position to make sense of the report. Occasionally, we might even be able to suggest a diagnostic or treatment option that may be appropriate for the patient. That’s one of the goals with this program,” she said.

Hamid said one consult during the trial period of Genetics E-consult ended up with a detailed review and in-depth analysis of medical records and genomic test reports of multiple additional family members before the patient’s test could be properly interpreted.

“By the time Janet reported her findings, it was for not only the patient but for the four other family members. That’s the degree of difficulty sometimes involved in interpreting results. If it’s taking us four days, you can imagine the time it would take an endocrinologist or an ophthalmologist, for example, requesting our services. Hopefully, with our help, the physician can have a better understanding of the molecular/genomic test results and have a better patient outcome down the road,” Hamid said.

Interestingly, few of these consults have resulted in the patient being referred to the VUDP for enrollment as the E-consult indicated that the patient might have a rare and undiagnosed disorder. The new program, announced in April, allows VUMC, already a national leader in assisting adults and children with undiagnosed diseases, to help more patients and families who are living with the often-dire consequences of an undiagnosed disease.

The E-consult service benefits greatly from VUMC’s world-recognized bioinformatics tools and of BioVU, a program that “banks” DNA and various types of genomic information to help researchers discover links between genes and disease. Patients have a choice to donate any leftover samples to BioVU by signing the BioVU consent form during check-in at a VUMC outpatient clinic. The samples are linked to corresponding electronic health records from which identifying information has been scrubbed.

For example, if an ophthalmologist orders a molecular test for a patient losing vision and there are 20 genes linked to types of retinopathies, and the report finds a rare variant, but it’s unclear if it’s disease causing because it hasn’t been reported in any patient, BioVU allows the team to go back and look at records to see if other patients with retinopathies who had genetic testing done at Vanderbilt tested positive with the same rare variant or another rare variant in the same gene.

“If such a connection is found, it increases the likelihood that the rare variant in the report might be disease-causing allowing us to tell the physician, ‘We think you have the answer.’ It’s yet another unique Vanderbilt tool that can help us provide better interpretations to the physicians who ask us for help,” Hamid said.

E-consult is now available to all VUMC clinical areas. For more information, contact Talbert at She is also available to give a short presentation to clinical areas within VUMC about how to utilize the new service.