Whole Exome Sequencing denials in California external review

What the reviewers wrote

Where the denial was overturned

Nature of Statutory Criteria/Case Summary: The parent of a 17-year-old enrollee has requested authorization and coverage for whole exome sequencing (WES) for evaluation of the enrollee’s common variable immune deficiency, granulomatous lymphcytic interstitial lung disease (GLIID), and oxalate distal neuropathy. Findings: 2/3 of the physician reviewers found that WES is a technology whereby the portion of the genome consisting of coding sequences is analyzed to look for variants that may explain the patient’s phenotype. Clinical indications for WES are a suspected genetic disorder based on signs and symptoms, with no known single gene condition fitting the phenotype. The utility of WES for gene discovery to identify the genetic cause of well-characterized specific phenotypes has been demonstrated in the peer-reviewed medical literature.

Nature of Statutory Criteria/Case Summary: An enrollee has requested authorization and coverage for gene testing. This patient’s provider has recommended whole exome sequencing to assist in this patient’s diagnosis and treatment given his history of autism, intellectual disability, syncope, hallucinations, and arachnoid cyst. Whole exome sequencing is a comprehensive test, which identifies changes in a patient’s DNA that are causative or related to their medical concerns. In contrast to current sequencing tests that analyze one gene or small groups of related genes, exome sequencing analyzes the exons or coding regions of over 20,000 genes. Neurodevelopmental disorders are often complex clinical scenarios attributed to single-gene mutations that may be detected through exome sequencing.

Where the denial was upheld

Nature of Statutory Criteria/Case Summary: An enrollee has requested authorization and coverage for full exome sequencing (genetic test) services. Findings: The physician reviewer found that American College of Medical Genetics and Genomics (ACMG) states, “Major advances in DNA sequencing technology have made it possible to do large-scale sequencing, up to and including whole-genome sequencing, in an effort to identify a gene mutation that may provide a diagnosis for a patient with an abnormal phenotype.” The ACMG definitions note, “Whole-genome sequencing (WGS) implies the determination of the sequence of most of the DNA content comprising the entire genome of an individual…The ‘exome’ is the component of the genome that predominantly encodes protein.

Findings: The physician reviewer found that Nature of Statutory Criteria/Case Summary: A patient has requested authorization and coverage for genetic testing.Whole-exome sequencing is typically reserved for patients with early-onset, severe, or syndromic features involving multiple organ systems or a strong suspicion of a monogenic or rare disorder after more targeted testing has been exhausted. On review of this patient’s records, there is a lack of documentation of early-onset or syndromic presentation that warrants whole-exome sequencing. In addition, the patient’s records do not document that a targeted maturity-onset diabetes of the young (MODY) panel, familial hypercholesterolemia panel, or other tiered genetic tests have been completed as a first-line approach.

These outcomes describe eligible cases completed through California DMHC’s Independent Medical Review program. They do not estimate the chance that an internal appeal, an external review in another jurisdiction, or your individual case will succeed. Use the record to identify evidence patterns involving Whole Exome Sequencing, then check the rights and deadlines that apply to your plan.