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Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex
Author(s) -
HoogeveenWesterveld Marianne,
Wentink Marjolein,
van den Heuvel Diana,
Mozaffari Melika,
Ekong Rosemary,
Povey Sue,
den Dunnen Johan T.,
Metcalfe Kay,
Vallee Stephanie,
Krueger Stefan,
Bergoffen JoAnn,
Shashi Vandana,
Elmslie Frances,
Kwiatkowski David,
Sampson Julian,
Vidales Concha,
Dzarir Jacinta,
GarciaPlanells Javier,
Dies Kira,
MaatKievit Anneke,
van den Ouweland Ans,
Halley Dicky,
Nellist Mark
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21451
Subject(s) - tsc1 , tsc2 , tuberous sclerosis , biology , genetics , gene , missense mutation , phenotype , pathology , medicine , pi3k/akt/mtor pathway , apoptosis
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. Hum Mutat 32:1–12, 2011. © 2011 Wiley‐Liss, Inc.