Skip to main content
Premium Trial:

Request an Annual Quote

Counsyl Offers NGS-Based Carrier Screening Test as Reflex to Array-Based Test

Premium

Counsyl has begun offering a next-generation sequencing-based expanded carrier screening test to early access users with a full commercial launch planned for the end of the second quarter this year.

The test complements Counsyl's array-based genotyping test, which screens for around 400 variants in 100 disorders. The sequencing-based test screens for the same disorders, but can detect over 10,000 mutations.

While it is still early, the company has seen its early access customers using it primarily as a follow-up to the genotyping test. "The rationale [for using the NGS test] is that in the initial stages we're seeing reflex testing," CEO Ramji Srinivasan told Clinical Sequencing News. For example, if a prospective mother has a positive result on the array-based test, the physician will screen the prospective father with the sequencing-based test to ensure that rarer variants are detected, he explained.

The NGS test targets and sequences the coding regions and flanking intronic regions of 98 genes. Two of the genes, GBA and IDUA, are not well-covered by sequencing and are therefore still assessed by genotyping methods, Counsyl's Chief Scientific Officer Eric Evans explained.

The advantage of converting from genotyping to sequencing is that the test has a higher rate of detection because it screens for many more variants, Srinivasan said.

The firm uses the Illumina HiSeq 2000 for sequencing and multiplexes 96 samples per run.

Counsyl charges patients with insurance an out-of-pocket maximum of $299 for the NGS version and $99 for the genotyping test, by pre-verifying with the patient's insurance company before sending a bill.

"If we see that the patient responsibility would be more than our max out-of-pocket program price, we skip insurance entirely and just bill the patient" the out-of-pocket maximum, Srinivasan said.

Uninsured patients are charged $999 for the NGS test and $599 for the genotyping test. Turnaround time is three to four weeks.

The company also provides genetic counseling, which is included in the price of the test. It has genetic counselors on staff who provide post-test counseling, Srinivasan said.

Jim Goldberg, an obstetrician at San Francisco Perinatal Associates offers Counsyl's genotyping test and is an early access customer of the company's sequencing-based version.

He told CSN that his patients have been primarily ordering it as a follow-up or reflex test, but he thinks that eventually it will be ordered as a primary test.

"In patients that come up positive on Counsyl's traditional carrier test, during the counseling session we offer them [the sequencing-based test]," he said.

Not all couples opt for the sequencing-based test, however. "We quote them a residual risk and many couples are perfectly happy with that," he said. Going forward, he said that better understanding by both the physician and patient of residual risk and what it means will be critical to test adoption and for insuring proper use of the test.

In the past, Goldberg had done follow-up testing on patients with positive results using Sanger sequencing, which detected fewer variants and was more expensive. The NGS test "offers a nice inexpensive option for patients," he said.

So far only a handful of patients have received the test, he said, so it is too early to judge performance of the test or its uptake.

Counsyl is not the only company offering NGS expanded carrier screening tests. Good Start Genetics has been offering a test for a little over one year that screens for mutations related to 23 disorders recommended in guidelines set by the American Congress of Obstetricians & Gynecologists and the American College of Medical Genetics and Genomics, as well as societies supporting the Ashkenazi Jewish population (CSN 2/13/2013).

Srinivasan said the main difference between the two companies is the sheer number of disorders each firm's test assesses.

Counsyl's test includes all the disorders recommended by ACMG and ACOG. It also includes other serious disorders that can be diagnosed prenatally.

Criteria for adding disorders include high-risk for significantly shortened life expectancy, having limited or no treatment options or an increased risk for intellectual disability, Srinavasan said. The company is now in the process of adding around 20 more disorders to its sequencing-based panel, he said.

In terms of customers, Counsyl is targeting obstetric and fetal medicine specialists, who will likely have high risk patients, as well as in vitro fertilization clinics.

Srinivasan said that while he expects the NGS-based test to gain traction over the genotyping test, he thinks that there will be a market for genotyping for several years and that the two technologies will co-exist.

San Francisco Perinatal's Goldberg agreed and said that one barrier to adoption of the sequencing based test is interpretation.

"That will be a continual problem until our databases get better," he said. For instance, while the NGS test may have a higher detection rate because it assesses more variants, it will also discover many more variants of unknown significance. Goldberg said that some patients have already expressed concern about this and what to do if a variant of unknown significance is found in a gene associated with a serious disorder.

"For many patients, they decide not to go ahead with the testing because of the possibility of variants of unknown significance," he said. "It certainly is an issue … and for many patients, it's a deterrent," he said.

Screening for over 100 disorders at once has also changed the way Goldberg provides genetic counseling to his patients. When offering screening for only a handful of disorders, pre-test counseling involved a detailed explanation of every disorder that would be tested for, he said. But with expanded carrier screening, there are too many disorders for that to be practical. "We had to shift," he said. Now, the pre-test counseling doesn't focus on the specific diseases, but rather the ability of the test and potential outcomes.

Post-test counseling will focus on the specifics of any disorder for which the patient is positive as well as what the result means in terms of risk, since different variants and disorders have different levels of risk associated with them, he said.

The Scan

Driving Malaria-Carrying Mosquitoes Down

Researchers from the UK and Italy have tested a gene drive for mosquitoes to limit the spread of malaria, NPR reports.

Office Space to Lab Space

The New York Times writes that some empty office spaces are transforming into lab spaces.

Prion Pause to Investigate

Science reports that a moratorium on prion research has been imposed at French public research institutions.

Genome Research Papers on Gut Microbe Antibiotic Response, Single-Cell RNA-Seq Clues to Metabolism, More

In Genome Research this week: gut microbial response to antibiotic treatment, approach to gauge metabolic features from single-cell RNA sequencing, and more.