caa a22 4500 605544409 CHVBK 20210128100931.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10897-015-9875-z doi (NATIONALLICENCE)springer-10.1007/s10897-015-9875-z A Novel von Hippel Lindau Gene Intronic Variant and Its Reclassification from VUS to Pathogenic: the Impact on a Large Family [Elektronische Daten] [A. Sexton, L. Rawlings, G. McKavanagh, K. Simons, I. Winship] We present a case where a variant of uncertain significance in the von Hippel Lindau syndrome gene (VHL) was identified in a proband with haemangioblastoma, and in a second degree relative with phaeochromocytoma. Initial uncertainty due to the unclear nature of the variant created psychosocial challenges for this family, in which four other genetic conditions were also present. Subsequent RNA studies confirmed this as a novel pathogenic mutation affecting splicing of exon 2. A third relative has since been diagnosed with haemangioblastoma. We suggest that this mutation possibly has reduced penetrance as there was no history of haemangioblastoma, renal tumours (apart from small cysts) or other VHL tumours among five mutation positive and seven untested adult relatives at 50% risk of the VHL mutation (average age 46years, range 18-70years). This case presents a novel VHL splicing mutation and highlights the psychosocial and medical value of additional laboratory studies on uncertain variants for individuals, their families and for the health professionals providing advice and counseling. National Society of Genetic Counselors, Inc., 2015 Genetic counseling nationallicence von Hippel Lindau syndrome nationallicence Splicing mutation nationallicence VUS nationallicence Uncertainty nationallicence Sexton A. Familial Cancer Centre, Royal Melbourne Hospital, 2-Centre, Grattan St, 3050, Parkville, VIC, Australia aut Rawlings L. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut McKavanagh G. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut Simons K. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut Winship I. Familial Cancer Centre, Royal Melbourne Hospital, 2-Centre, Grattan St, 3050, Parkville, VIC, Australia aut Journal of Genetic Counseling Springer US; http://www.springer-ny.com 24/6(2015-12-01), 882-889 1059-7700 24:6<882 2015 24 10897 https://doi.org/10.1007/s10897-015-9875-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10897-015-9875-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sexton A. Familial Cancer Centre, Royal Melbourne Hospital, 2-Centre, Grattan St, 3050, Parkville, VIC, Australia aut NATIONALLICENCE 700 1- Rawlings L. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- McKavanagh G. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Simons K. SA Pathology, Genetics & Molecular Pathology, Frome Rd, 5000, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Winship I. Familial Cancer Centre, Royal Melbourne Hospital, 2-Centre, Grattan St, 3050, Parkville, VIC, Australia aut NATIONALLICENCE 773 0- Journal of Genetic Counseling Springer US; http://www.springer-ny.com 24/6(2015-12-01), 882-889 1059-7700 24:6<882 2015 24 10897