BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

Amanda B Spurdle; Phillip J Whiley; Bryony Thompson; Bingjian Feng; Sue Healey; Melissa A Brown; Christopher Pettigrew; Christi J Van Asperen; Margreet G E M Ausems; Anna A Kattentidt-Mouravieva; Ans M W van den Ouweland; Annika Lindblom; Maritta H Pigg; Rita K Schmutzler; Christoph Engel; Alfons Meindl; Sandrine Caputo; Olga M Sinilnikova; Rosette Lidereau; Fergus J Couch; Lucia Guidugli; Thomas van Overeem Hansen; Mads Thomassen; Diana M Eccles; Kathy Tucker; Javier Benitez; Susan M Domchek; Amanda E Toland; Elizabeth J Van Rensburg; Barbara Wappenschmidt; Åke Borg; Maaike P G Vreeswijk; David E Goldgar; kConFab

doi:10.1136/jmedgenet-2012-101037

BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

Amanda B Spurdle, Phillip J Whiley, Bryony Thompson, Bingjian Feng, Sue Healey, Melissa A Brown, Christopher Pettigrew, Christi J Van Asperen, Margreet G E M Ausems, Anna A Kattentidt-Mouravieva, Ans M W van den Ouweland, Annika Lindblom, Maritta H Pigg, Rita K Schmutzler, Christoph Engel, Alfons Meindl, Sandrine Caputo, Olga M Sinilnikova, Rosette Lidereau, Fergus J CouchLucia Guidugli, Thomas van Overeem Hansen, Mads Thomassen, Diana M Eccles, Kathy Tucker, Javier Benitez, Susan M Domchek, Amanda E Toland, Elizabeth J Van Rensburg, Barbara Wappenschmidt, Åke Borg, Maaike P G Vreeswijk, David E Goldgar, kConFab

Department of Genomic Medicine

100 Citations (Scopus)

Abstract

Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer.

Original language	English
Journal	Journal of Medical Genetics
Volume	49
Issue number	8
Pages (from-to)	525-32
Number of pages	8
ISSN	0022-2593
DOIs	https://doi.org/10.1136/jmedgenet-2012-101037
Publication status	Published - 2012

Keywords

Aged
BRCA1 Protein
Breast Neoplasms
Female
Genetic Predisposition to Disease
Genetic Testing
Genotyping Techniques
HEK293 Cells
Humans
Likelihood Functions
Mutation
Ovarian Neoplasms
Pedigree
Penetrance
Predictive Value of Tests
Risk Factors
Transcriptional Activation

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Spurdle, A. B., Whiley, P. J., Thompson, B., Feng, B., Healey, S., Brown, M. A., Pettigrew, C., Van Asperen, C. J., Ausems, M. G. E. M., Kattentidt-Mouravieva, A. A., van den Ouweland, A. M. W., Lindblom, A., Pigg, M. H., Schmutzler, R. K., Engel, C., Meindl, A., Caputo, S., Sinilnikova, O. M., Lidereau, R., ... kConFab (2012). BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk. Journal of Medical Genetics, 49(8), 525-32. https://doi.org/10.1136/jmedgenet-2012-101037

Spurdle, AB, Whiley, PJ, Thompson, B, Feng, B, Healey, S, Brown, MA, Pettigrew, C, Van Asperen, CJ, Ausems, MGEM, Kattentidt-Mouravieva, AA, van den Ouweland, AMW, Lindblom, A, Pigg, MH, Schmutzler, RK, Engel, C, Meindl, A, Caputo, S, Sinilnikova, OM, Lidereau, R, Couch, FJ, Guidugli, L, Hansen, TVO, Thomassen, M, Eccles, DM, Tucker, K, Benitez, J, Domchek, SM, Toland, AE, Van Rensburg, EJ, Wappenschmidt, B, Borg, Å, Vreeswijk, MPG, Goldgar, DE & kConFab 2012, 'BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk', Journal of Medical Genetics, vol. 49, no. 8, pp. 525-32. https://doi.org/10.1136/jmedgenet-2012-101037

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title = "BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk",

abstract = "Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer.",

keywords = "Aged, BRCA1 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genetic Testing, Genotyping Techniques, HEK293 Cells, Humans, Likelihood Functions, Mutation, Ovarian Neoplasms, Pedigree, Penetrance, Predictive Value of Tests, Risk Factors, Transcriptional Activation",

author = "Spurdle, \{Amanda B\} and Whiley, \{Phillip J\} and Bryony Thompson and Bingjian Feng and Sue Healey and Brown, \{Melissa A\} and Christopher Pettigrew and \{Van Asperen\}, \{Christi J\} and Ausems, \{Margreet G E M\} and Kattentidt-Mouravieva, \{Anna A\} and \{van den Ouweland\}, \{Ans M W\} and Annika Lindblom and Pigg, \{Maritta H\} and Schmutzler, \{Rita K\} and Christoph Engel and Alfons Meindl and Sandrine Caputo and Sinilnikova, \{Olga M\} and Rosette Lidereau and Couch, \{Fergus J\} and Lucia Guidugli and Hansen, \{Thomas van Overeem\} and Mads Thomassen and Eccles, \{Diana M\} and Kathy Tucker and Javier Benitez and Domchek, \{Susan M\} and Toland, \{Amanda E\} and \{Van Rensburg\}, \{Elizabeth J\} and Barbara Wappenschmidt and {\AA}ke Borg and Vreeswijk, \{Maaike P G\} and Goldgar, \{David E\} and kConFab",

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doi = "10.1136/jmedgenet-2012-101037",

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AU - Spurdle, Amanda B

AU - Whiley, Phillip J

AU - Thompson, Bryony

AU - Feng, Bingjian

AU - Healey, Sue

AU - Brown, Melissa A

AU - Pettigrew, Christopher

AU - Van Asperen, Christi J

AU - Ausems, Margreet G E M

AU - Kattentidt-Mouravieva, Anna A

AU - van den Ouweland, Ans M W

AU - Lindblom, Annika

AU - Pigg, Maritta H

AU - Schmutzler, Rita K

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Caputo, Sandrine

AU - Sinilnikova, Olga M

AU - Lidereau, Rosette

AU - Couch, Fergus J

AU - Guidugli, Lucia

AU - Hansen, Thomas van Overeem

AU - Thomassen, Mads

AU - Eccles, Diana M

AU - Tucker, Kathy

AU - Benitez, Javier

AU - Domchek, Susan M

AU - Toland, Amanda E

AU - Van Rensburg, Elizabeth J

AU - Wappenschmidt, Barbara

AU - Borg, Åke

AU - Vreeswijk, Maaike P G

AU - Goldgar, David E

AU - kConFab

PY - 2012

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N2 - Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer.

AB - Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer.

KW - Aged

KW - BRCA1 Protein

KW - Breast Neoplasms

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Testing

KW - Genotyping Techniques

KW - HEK293 Cells

KW - Humans

KW - Likelihood Functions

KW - Mutation

KW - Ovarian Neoplasms

KW - Pedigree

KW - Penetrance

KW - Predictive Value of Tests

KW - Risk Factors

KW - Transcriptional Activation

UR - https://www.scopus.com/pages/publications/84866329098

U2 - 10.1136/jmedgenet-2012-101037

DO - 10.1136/jmedgenet-2012-101037

M3 - Journal article

C2 - 22889855

SN - 0022-2593

VL - 49

SP - 525

EP - 532

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 8

ER -

BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

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Keywords

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