We asked, and you answered! Here are the responses from this month’s “You Make the Call” question on referring patient whose bone marrow samples that came back with mutations for genetic counseling and germline testing.
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I would not refer either patient for genetic counseling, but would follow up every six months with the patient who has a TET2 mutation because it sounds like there could be a high risk for developing myelodysplastic syndromes or leukemia. For the second patient, the only appropriate intervention is reassurance.
Richard Lind, MD
Asheville, North Carolina
More information is needed before referring either patient for genetic counseling or germline evaluation: What are the specific variants? How are the variants classified (e.g., likely pathogenic/pathogenic, variant of uncertain significance [VUS], etc.)? Have these variants been reported in the germline before? ClinVar is an excellent resource to determine the answer to the last question.
If these variants are classified as benign, VUS, or are known to be common benign germline polymorphisms, then I do not think that further genetic evaluation is necessary. In contrast, if the variant is known to be pathogenic in the germline (e.g., EGFR T790M), then a genetics referral would be appropriate.
Lauren Banaszak, MD
Madison, Wisconsin
In the first case, if the patient is elderly, a TET2 mutation close to 50% could be clonal hematopoiesis of indeterminate potential. In the second case, a positive mutation for an unclear variant in EGFR close to 50% could be considered a germline mutation; however, it would not be related to a propensity for hematologic malignancy but to oncologic diseases of epithelial or epidermal origin. Here, I would refer the patient to an onco-genetic counseling service and follow the monoclonal paraproteinemia (IgA lambda).
Israel Bendit, MD, PhD
Sao Paulo, Brazil