title: Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.
abstract: The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In addition we identified eight putative splice site mutations (five TSC1 and three TSC2). The remaining 24 TSC1 and 34 TSC2 variants were classified as probably neutral.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.forename: Marjolein
authors.initials: M
authors.lastname: Wentink
authors.forename: Diana
authors.initials: D
authors.lastname: van den Heuvel
authors.forename: Melika
authors.initials: M
authors.lastname: Mozaffari
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ekong
authors.forename: Sue
authors.initials: S
authors.lastname: Povey
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Kay
authors.initials: K
authors.lastname: Metcalfe
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vallee
authors.forename: Stefan
authors.initials: S
authors.lastname: Krueger
authors.forename: JoAnn
authors.initials: J
authors.lastname: Bergoffen
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.forename: Frances
authors.initials: F
authors.lastname: Elmslie
authors.forename: David
authors.initials: D
authors.lastname: Kwiatkowski
authors.forename: Julian
authors.initials: J
authors.lastname: Sampson
authors.forename: Concha
authors.initials: C
authors.lastname: Vidales
authors.forename: Jacinta
authors.initials: J
authors.lastname: Dzarir
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Planells
authors.forename: Kira
authors.initials: K
authors.lastname: Dies
authors.forename: Anneke
authors.initials: A
authors.lastname: Maat-Kievit
authors.forename: Ans
authors.initials: A
authors.lastname: van den Ouweland
authors.forename: Dicky
authors.initials: D
authors.lastname: Halley
authors.forename: Mark
authors.initials: M
authors.lastname: Nellist
mesh_terms: D002478:Cells, Cultured; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins