TABLE 3.
Details of clinically actionable VUS reclassifications and resulting management change
| Patient No | Variant reclassification | Management change | Sex | Race | Cancer Diagnosis |
|---|---|---|---|---|---|
| Patient 1 | CHEK2 (VUS to LP) | Yes, began high risk screening using breast MRI | F | White | Unaffected |
| Patient 2 | BRCA2 (VUS to LP) | Yes, underwent BLM and RRSO | F | White | Breast |
| Patient 3 | BRCA2 (VUS to LP) | Yes, began mammography | F | White | Breast |
| Patient 4 | CHEK2 (VUS to LP) | Yes, began high risk screening for breast and ovarian cancers | F | White | Breast |
| Patient 5 | CHEK2 (VUS to LP) | Yes, began frequent colonoscopy per NCCN guidelines for CHEK2 | F | White | Breast |
| Patient 6 | BRCA1 (VUS to LP) | Yes, BLM in past; RRSO not covered by insurance; OC screening being performed now | F | Hispanic or Latino | Breast |
| Patient 7 | PTEN (VUS to P) | Yes, undergoing breast MRI post reclass; Not interested in prophylactic mastectomy | F | Hispanic or Latino | Colon |
| Patient 8 | CHEK2 (VUS to P) | Yes, began breast MRI; Already had lumpectomy, Not interested in prophylactic mastectomy | F | White | Breast |
| Patient 9 | BRCA1 (VUS to LP) | Yes, underwent BLM after VUS upgrade | F | White | Breast |
| Patient 10 | CHEK2 (VUS to LP) | Yes, more frequent breast cancer screening | F | White | Breast |
| Patient 11 | ATM (VUS to LP) | Yes, underwent BLM | F | White | Breast |
| Patient 12 | BRCA1 (VUS to LP) | Yes, began frequent mammography | F | Black | Breast |
| Patient 13 | RAD51D (VUS to P) | No, previously underwent TAH/BSO for fallopian tube cancer | F | White | Fallopian tube |
| Patient 14 | CHEK2 (VUS to LP) | No, previously underwent left mastectomy due to cancer | M | White | Breast |
| Patient 15 | BRCA2 (VUS to LP) | No. Already post BLM and BSO as VUS classified as LP at a different lab | F | White | None |
| Patient 16 | CHEK2 (VUS to LP) | No. Mastectomy previously due to cancer and undergoing annual mammography (no MRI) at time of upgrade | F | White | Breast |
| Patient 17 | TP53 (VUS to LP) | No, previously underwent BLM; part of screening study for other cancers from before reclassification | F | White | Leukemia |
| Patient 18 | BRCA2 (VUS to LP) | No, previously underwent BSO; not interested in BLM; breast MRI planned but none performed yet | F | Black | Unaffected |
| Patient 19 | MLH1 (VUS to LP) | No, already underwent TAHBSO | F | Other | Breast |
| Patient 20 | MUTYH (VUS to LP) | No, undergoing colonoscopies every 5 years at time of upgrade | M | White | Unaffected |
| Patient 21 | ATM (VUS to LP) | No, previously underwent BLM and TLH BSO | F | White | Breast |
| Patient 22 | MSH2 (VUS to LP) | No, surgical colectomy in past; plans for more frequent colonoscopy but not enough time since reclassification | M | White | Sarcoma |
| Patient 23 | RAD51C (VUS to LP) | NA, already underwent TAHBSO due to OC; deceased before upgrade | F | White | Ovary |
| Patient 24 | NBN (VUS to P) | NA, Patient deceased before upgrade | M | White | Pancreas |
| Patient 25 | CHEK2 (VUS to LP) | Unknown, no follow‐up data after reclassification | F | Hispanic or Latino | Breast |
| Patient 26 | BARD1 (VUS to LP) | Unknown, no follow‐up data after reclassification | F | White | Unknown |
| Patient 27 | TP53 (VUS to LP) | Unknown, no follow‐up data after reclassification | M | Other | Unaffected |
Abbreviations: BC, breast cancer; BLM, bilateral mastectomy; MRI, magnetic resonance imaging; OC, ovarian cancer; TAHBSO, total abdominal hysterectomy bilateral salpingo oophorectomy; VUS, variant of uncertain significance; Sites 1, 2, 3, and 4 refer to Baptist, Cooper, MD Anderson, and OhioHealth respectively.