Abstract
Purpose :
To compare genetic test results performed by two different free-of-charge sponsored genetic testing panels for inherited retinal disease (IRD).
Methods :
Genetic test reports of patients at the USC Roski Eye Institute and Los Angeles General Medical Center were reviewed for reported variants. These reports were generated by two different laboratories, each of which tested a panel of IRD genes. The Blueprint Genetics (BG) panel was sponsored by the Foundation Fighting Blindness (FFB) and the Invitae panel was sponsored by Spark Therapeutics. The panels have 264 genes in common; with 66 genes in the Invitae and 60 genes in the BG panels.
Results :
The cohort includes 109 patients underwent testing with the Invitae panel and 107 patients with the BG panel, all with clinical suspicion of IRD. The mean age was 47.2 ± 17.4 years in the Invitae cohort and 50.0 ± 16.7 years in the BG cohort. The total number of positive tests explaining the clinical phenotype was 36.7% for Invitae and 42.1% for BG. The mean number of amendments per patient was 0.54 ± 0.80 in the Invitae group (total: 71) and 0.03 ± 0.17 in the BG group (total: 4). In the Invitae group, 23 patients had one amendment, 15 patients had two amendments, and 2 patients had three amendments. The mean time to amendment was 600.3 ± 362.8 days (range: 48-1255 days) for Invitae and 655.7 ± 224.1 days (range: 427-875 days) for BG. Of the Invitae amendments, 66.2% switched a variant of unknown significance (VUS) to benign; 21.1% changed a VUS to pathogenic or likely pathogenic, 11.3% switched likely pathogenic to pathogenic, and 1.4% switched benign to VUS. In the BG group, 75% of amendments changed a VUS to pathogenic, and 25% of amendments changed a likely pathogenic to pathogenic. One patient in the Invitae group was a carrier for a gene (CLN8) that was not included in the BG panel. Two patients in the BG group had pathogenic mutations (MT-ATP6, MT-ND1), and one patient was a carrier (MMAHC) in genes not included in Invitae’s panel.
Conclusions :
Free-of-charge sponsored genetic testing panels can provide genetic diagnoses to patients with clinical IRD. As our understanding of the genetics behind IRD expands, reports are updated and VUS defined. However, providers should be cautious about assuming VUS are pathogenic in cases that fit the clinical picture, as they are more likely to be reported benign than pathogenic in follow-up amendments.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.