Do you need a positive control?

At Invitae, we do not accept family member samples for positive control when the variant is a single nucleotide variant or multi-exon copy number variation. Instead, we request a copy of the family member's report with the relevant variant information (coding DNA and protein coordinates) included. Positive controls are not needed in these cases because we use full next-generation sequencing and del/dup assay for all testing, including family variant testing. We do not use a PCR/Sanger test like some other labs do. Therefore, the assay that we use for family variant testing (FVT) is fully validated for all of the genes we routinely test, and our ability to detect variants of this class using this assay has been well established. Furthermore, our capture pull-down is not susceptible to the kind of allele-dropout that can be an issue with PCR/Sanger-based mutation detection. For all of these reasons, a positive control is not required/accepted for high-confidence FVT testing.