RET Y791F - GET-Evidence

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RET Y791F

(RET Tyr791Phe)


You are viewing an old version of this page that was saved on November 27, 2013 at 11:23am by Madeleine Ball.

Edited in this revision:

Short summary

 

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr10:43613908: 0.1% (14/10758) in EVS
  • Frequency shown in summary reports: 0.1% (14/10758)

Publications
 

Berndt I, Reuter M, Saller B, Frank-Raue K, Groth P, Grussendorf M, Raue F, Ritter MM, Höppner W. A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A. J Clin Endocrinol Metab. 1998 Mar;83(3):770-4. PubMed PMID: 9506724.

 

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peçzkowska M, Szmigielski C, Eng C; Freiburg-Warsaw-Columbus Pheochromocytoma Study Group. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 May 9;346(19):1459-66. PubMed PMID: 12000816.

 

Fitze G, Schierz M, Bredow J, Saeger HD, Roesner D, Schackert HK. Various penetrance of familial medullary thyroid carcinoma in patients with RET protooncogene codon 790/791 germline mutations. Ann Surg. 2002 Nov;236(5):570-5. PubMed PMID: 12409662; PubMed Central PMCID: PMC1422614.

 

Jindrichová S, Vcelák J, Vlcek P, Neradilová M, Nemec J, Bendlová B. Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic. J Endocrinol. 2004 Nov;183(2):257-65. PubMed PMID: 15531714.

 

Frank-Raue K, Rondot S, Hoeppner W, Goretzki P, Raue F, Meng W. Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism. J Clin Endocrinol Metab. 2005 Jul;90(7):4063-7. Epub 2005 May 3. Erratum in: J Clin Endocrinol Metab. 2005 Oct;90(10):5575. PubMed PMID: 15870131.

 

Baumgartner-Parzer SM, Lang R, Wagner L, Heinze G, Niederle B, Kaserer K, Waldhäusl W, Vierhapper H. Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma? J Clin Endocrinol Metab. 2005 Nov;90(11):6232-6. Epub 2005 Aug 23. PubMed PMID: 16118333.

 

Dvorakova S, Vaclavikova E, Ryska A, Cap J, Vlcek P, Duskova J, Kodetova D, Holub V, Novak Z, Bendlova B. Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds. Exp Clin Endocrinol Diabetes. 2006 Apr;114(4):192-6. PubMed PMID: 16705552.

 

Vaclavikova E, Dvorakova S, Sykorova V, Bilek R, Dvorakova K, Vlcek P, Skaba R, Zelinka T, Bendlova B. RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest. Endocrine. 2009 Dec;36(3):419-24. doi: 10.1007/s12020-009-9242-7. Epub 2009 Oct 14. PubMed PMID: 19826964.

Molecular genetic analysis was performed in 276 families with medullary thyroid carcinoma (31 familial and 245 apparently sporadic), 29 patients with apparently sporadic pheochromocytoma, and 122 families with Hirschsprung’s disease (a total of 427 families and unrelated individuals). The RET Y791F variant was found in 31 patients from 10 families — an allele frequency of 1.2% in these cases. The authors do not list any controls to compare this to.

If EVS data were considered a control group, these observations diverge from EVS data with a statistical significance of p=3.2 * 10^-6.

Genomes
 

Other external references
 

    GeneTests
  • GeneTests records for the RET gene
    Hirschsprung Disease
    Multiple Endocrine Neoplasia Type 2
    RET-Related Hirschsprung Disease
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RET
    PolyPhen-2
  • Score: 0.402 (possibly damaging)
    Web search results (579 hits -- see all)
  • JCEM -- eLetters for Erlic et al., 95 (1) 308-313
    Pathogenicity of the p.Tyr791Phe RET Germline Mutation. Andreas Machens, Henning Dralle ... 2007 Y791F RET mutation and early onset of medullary thyroid ...
    jcem.endojournals.org/cgi/eletters/95/1/308
  • New Products / Carna Biosciences Inc.
    RET[G691S] (Custom Profiling Comparative Inhibitory Activity) RET[G691S] (Custom ... RET[Y791F] (Custom Profiling Comparative Inhibitory Activity) ...
    www.carnabio.com/output/newproducts_en.xml
  • Primary hyperparathyroidism as the leading symptom in a ...
    Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation. ... a mutation (Y791F, TAT-->TTT) in exon 13 of the RET proto-oncogene. ...
    www.ncbi.nlm.nih.gov/pubmed/16356097
  • CORDIS: Technology Marketplace: Results
    Abstract: The proto-oncogene RET a member of the tyrosine-kinase receptor its ... The RET Y791F mutation may be a common genetic abnormality underlying ...
    cordis.europa.eu/fetch?CALLER=NEW_RESU_TM&ACTION=D&...
  • Fenotypes in patients with Y791F mutation of RET protooncogene
    Mutation Y791F of RET protooncogene is a well known mutation so far described in families with FMTC and familial pheochromocytoma in one family. ...
    www.endocrine-abstracts.org/ea/0016/ea0016p339.htm
  • RET-Familial Medullary Thyroid Carcinoma Mutants Y791F and ...
    The RET proto-oncogene encodes a receptor tyrosine kinase. whose dysfunction plays a ... properties of two FMTC-associated RET mutations, Y791F and ...
    cancerres.aacrjournals.org/cgi/reprint/65/5/1729.pdf
  • RET-Familial Medullary Thyroid Carcinoma Mutants Y791F and ...
    RET-Familial Medullary Thyroid Carcinoma Mutants Y791F and S891A Activate a Src/JAK/STAT3 Pathway, Independent of Glial Cell Line–Derived Neurotrophic Factor ...
    cancerres.aacrjournals.org/cgi/content/full/65/5/1729
  • High Penetrance of Pheochromocytoma Associated with the Novel ...
    Patients: Sixteen patients from four unrelated families and harboring the C634Y/Y791F double RET germline mutation were included in the study. ...
    jcem.endojournals.org/cgi/content/abstract/jc.2009-1355v1
  • Transcriptome analysis in mouse tumors induced by Ret-MEN2 ...
    Activating mutations in the Ret proto-oncogene are responsible for occurrence of multiple ... NIH-RET(MEN2B) (A883F, M918T) and NIH-RET(FMTC) (Y791F)-specific ...
    erc.endocrinology-journals.org/cgi/content/full/16/1/211
  • Carna Biosciences, Inc.
    スピンオフ・バイオベンチャー企業。大手製薬企業の研究部門が母体となって2003年4月に設立されたバイオベンチャー企業です。細胞内、細胞間シグナルの研究を行い、革新的な創薬ターゲットおよび高価値の医薬品候補化合物をグローバルな製薬企業へ提供する先導企業になる。
    www.carnabio.com

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 5

Edit history
 

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