Invitae’s variant classifications are based on a rigorous, logical, and reproducible assessment of available evidence. Our method of variant interpretation enables us to be comprehensive in our review of the available literature and evidence, transparent in our logic and our conclusions, and clear in our explanations.
Our systematic process adheres closely to the recommendations from the American College of Medical Genetics (ACMG) and was published in Genetics in Medicine, the official journal of ACMG. It represents the industry standard among clinical genetic testing laboratories.
In addition, Invitae’s state-of-the-art Functional Modeling Platform (FMP) provides clarity for patients with variants of uncertain significance (VUS). By pulling in many lines of evidence from both lab experiments and computational analyses, FMP can accurately predict how some VUS will affect gene function. For 1 in 40 (or 2.5%) of Invitae patients, that means we can provide a more definitive variant classification (benign, likely benign, likely pathogenic, or pathogenic), rather than a VUS. Learn more >
Invitae confirms clinically significant findings that do not meet our stringent NGS quality metrics, using orthogonal technologies including Sanger sequencing, PacBio long read sequencing, aCGH (array comparative genome hybridization), and MLPA (multiplex ligation-dependent probe amplification). To guard against false negative results, Invitae runs multiple overlapping assays to redundantly target each variant.
Additionally, Invitae confirms CNV events by performing aCGH with a custom designed exon-focused microarray. This is the industry standard technique for these events.
Invitae submits all clinically reported variants, their classifications (i.e., pathogenic, benign, VUS, etc.) and the underlying evidence for and against pathogenicity to ClinVar. The sharing of data through ClinVar is unique in that it allows ongoing:
No other mechanism, including published scientific papers, solves these important problems. We encourage you to ask other testing providers if they share all variants, classifications, and evidence to public databases. Learn more >