A NOVEL GERMLINE TP53 MUTATION IN A PATIENT WITH LI-FRAUMENI SYNDROME -
RESOLVING A VARIANT OF UNCERTAIN SIGNIFICANCE
Abstract
Increasing availability of genomic testing poses new challenges to
clinicians, particularly where variant interpretation from commercial
sources may be equivocal. We report a patient with recurrent
rhabdomyosarcoma and subsequent bilateral breast cancer who was found to
harbor a previously undescribed germline TP53 sequence alteration
annotated by the commercial laboratory as a variant of uncertain
significance (VUS). By investigating publically available databases of
aggregated normal germline and malignant somatic genomic sequences, we
conclude that this missense variant, c.476C>T (p.A159V), is
a novel, pathogenic Li-Fraumeni syndrome mutation, and illustrate the
utility of these resources in clinical pediatric hematology and oncology
practice.