Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex

Marianne Hoogeveen - Westerveld; Marjolein Wentink; Diana Heuvel; M Mozaffari; R Ekong; S Povey; JT Dunnen; K Metcalfe; S Vallee; S Krueger; J Bergoffen; V Shashi; F Elmslie; D Kwiatkowski; J Sampson; C Vidales; J Dzarir; J Garcia-Planells; K Dies; JA Maat-Kievit; Ans van den Ouweland; Dicky Halley; Mark Nellist

doi:10.1002/humu.21451

Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex

Marianne Hoogeveen - Westerveld, Marjolein Wentink, Diana Heuvel, M Mozaffari, R Ekong, S Povey, JT Dunnen, K Metcalfe, S Vallee, S Krueger, J Bergoffen, V Shashi, F Elmslie, D Kwiatkowski, J Sampson, C Vidales, J Dzarir, J Garcia-Planells, K Dies, JA Maat-KievitAns van den Ouweland, Dicky Halley, Mark Nellist

Research output: Contribution to journal › Article › Academic › peer-review

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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. Hum Mutat 32: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.

Original language	English
Pages (from-to)	424-435
Number of pages	12
Journal	Human Mutation
Volume	32
Issue number	4
DOIs	https://doi.org/10.1002/humu.21451
Publication status	Published - 2011

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10.1002/humu.21451

http://hdl.handle.net/1765/34224

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Hoogeveen - Westerveld, M., Wentink, M., Heuvel, D., Mozaffari, M., Ekong, R., Povey, S., Dunnen, JT., Metcalfe, K., Vallee, S., Krueger, S., Bergoffen, J., Shashi, V., Elmslie, F., Kwiatkowski, D., Sampson, J., Vidales, C., Dzarir, J., Garcia-Planells, J., Dies, K., ... Nellist, M. (2011). Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex. Human Mutation, 32(4), 424-435. https://doi.org/10.1002/humu.21451

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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. Hum Mutat 32: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.",

author = "{Hoogeveen - Westerveld}, Marianne and Marjolein Wentink and Diana Heuvel and M Mozaffari and R Ekong and S Povey and JT Dunnen and K Metcalfe and S Vallee and S Krueger and J Bergoffen and V Shashi and F Elmslie and D Kwiatkowski and J Sampson and C Vidales and J Dzarir and J Garcia-Planells and K Dies and JA Maat-Kievit and {van den Ouweland}, Ans and Dicky Halley and Mark Nellist",

year = "2011",

doi = "10.1002/humu.21451",

language = "English",

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Hoogeveen - Westerveld, M, Wentink, M, Heuvel, D, Mozaffari, M, Ekong, R, Povey, S, Dunnen, JT, Metcalfe, K, Vallee, S, Krueger, S, Bergoffen, J, Shashi, V, Elmslie, F, Kwiatkowski, D, Sampson, J, Vidales, C, Dzarir, J, Garcia-Planells, J, Dies, K, Maat-Kievit, JA, van den Ouweland, A, Halley, D & Nellist, M 2011, 'Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex', Human Mutation, vol. 32, no. 4, pp. 424-435. https://doi.org/10.1002/humu.21451

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T1 - Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex

AU - Hoogeveen - Westerveld, Marianne

AU - Wentink, Marjolein

AU - Heuvel, Diana

AU - Mozaffari, M

AU - Ekong, R

AU - Povey, S

AU - Dunnen, JT

AU - Metcalfe, K

AU - Vallee, S

AU - Krueger, S

AU - Bergoffen, J

AU - Shashi, V

AU - Elmslie, F

AU - Kwiatkowski, D

AU - Sampson, J

AU - Vidales, C

AU - Dzarir, J

AU - Garcia-Planells, J

AU - Dies, K

AU - Maat-Kievit, JA

AU - van den Ouweland, Ans

AU - Halley, Dicky

AU - Nellist, Mark

PY - 2011

Y1 - 2011

N2 - 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: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.

AB - 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: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.

U2 - 10.1002/humu.21451

DO - 10.1002/humu.21451

M3 - Article

SN - 1059-7794

VL - 32

SP - 424

EP - 435

JO - Human Mutation

JF - Human Mutation

IS - 4

ER -

Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex

Abstract

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