PMID- 30869828
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 40
IP  - 6
DP  - 2019 Jun
TI  - Proposition of adjustments to the ACMG-AMP framework for the interpretation of 
      MEN1 missense variants.
PG  - 661-674
LID - 10.1002/humu.23746 [doi]
AB  - In 2015, the ACMG-AMP guidelines provided a general procedure for the objective 
      and reproducible classification of genomic variants. While the benefits of this 
      framework are of major importance, its adaptation for locus-specific use is 
      needed. Multiple Endocrine Neoplasia type 1 (MEN1) occurs due to inactivating 
      mutations in the tumour suppressor gene MEN1, including 20% of missense variants. 
      The classification of these variants may be extremely challenging. Here, we 
      compared the interpretation of the 122 MEN1 missense variants, identified in the 
      French population over the past 15 years by the TENGEN network (French 
      oncogenetics network of neuroendocrine tumors) versus by using the ACMG-AMP 
      guidelines, and analyzed the causes of discordance. A total of 59.8% of missense 
      variants were termed as (likely)-pathogenic variants by TENGEN versus only 28.7% 
      using ACMG-AMP guidelines. Actually, 53.4% (39/73) of TENGEN (likely)-pathogenic 
      variants were declassified in variant of uncertain significance (VUS) by using 
      ACMG-AMP guidelines, thereby affecting the clinical management of patients and 
      their families. Twenty of these ACMG-AMP VUS were found in patients with a 
      clinically authentic MEN1 disease. Here, TENGEN proposes adjustments to the 
      ACMG-AMP framework for the interpretation of MEN1 missense variants. These 
      propositions merge both the classification systems, and are particularly 
      interesting, as MEN1 is included in the ACMG secondary findings list for 
      reporting in clinical genomic sequencing.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Romanet, Pauline
AU  - Romanet P
AUID- ORCID: 0000-0003-1775-9569
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
FAU - Odou, Marie-Francoise
AU  - Odou MF
AD  - CHU Lille, Service de Biochimie et Biologie moleculaire "Hormonologie, 
      Metabolisme-Nutrition, Oncologie", F-59037 Lille, France.
FAU - North, Marie-Odile
AU  - North MO
AD  - Service de Genetique et Biologie Moleculaires, Hopital Cochin, Assistance 
      Publique - Hopitaux de Paris, 27 Rue du Faubourg Saint Jacques, Paris, France.
FAU - Saveanu, Alexandru
AU  - Saveanu A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
FAU - Coppin, Lucie
AU  - Coppin L
AD  - Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research 
      Center, F-59000 Lille, France.
FAU - Pasmant, Eric
AU  - Pasmant E
AD  - Service de Genetique et Biologie Moleculaires, Hopital Cochin, Assistance 
      Publique - Hopitaux de Paris, 27 Rue du Faubourg Saint Jacques, Paris, France.
FAU - Mohamed, Amira
AU  - Mohamed A
AD  - Laboratory of Molecular Biology, Hospital La Conception, Marseille, France.
FAU - Goudet, Pierre
AU  - Goudet P
AD  - Department of Endocrine Surgery, University Hospital of Dijon, and INSERM, U866, 
      Epidemiology and Clinical Research in Digestive Oncology Team, and INSERM, 
      CIC1432, Clinical Epidemiology Unit, University Hospital of Dijon, Clinical 
      Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon, France.
FAU - Borson-Chazot, Francoise
AU  - Borson-Chazot F
AD  - Hospices Civils de Lyon, Federation d'Endocrinologie, Universite Claude Bernard 
      Lyon 1, HESPER EA 7425, F-69008, Lyon, France.
FAU - Calender, Alain
AU  - Calender A
AD  - Genetics Department, Hospices Civils de LYON (HCL), University Hospital, East 
      Pathology Center, B-A3, 59 Bld Pinel, 69677, Bron Cedex, France.
FAU - Beroud, Christophe
AU  - Beroud C
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Departement de Genetique CHU La Timone 
      Enfants, Marseille, France.
FAU - Levy, Nicolas
AU  - Levy N
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Departement de Genetique CHU La Timone 
      Enfants, Marseille, France.
FAU - Giraud, Sophie
AU  - Giraud S
AD  - Genetics Department, Hospices Civils de LYON (HCL), University Hospital, East 
      Pathology Center, B-A3, 59 Bld Pinel, 69677, Bron Cedex, France.
FAU - Barlier, Anne
AU  - Barlier A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
LA  - eng
GR  - Not applicable/Institut National Du Cancer/International
GR  - not applicable/Ministere de la Sante de France/International
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190328
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Computational Biology/methods
MH  - France
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation, Missense
MH  - *Practice Guidelines as Topic
MH  - Proto-Oncogene Proteins/*genetics
MH  - Societies, Medical/organization & administration
MH  - Software
OTO - NOTNLM
OT  - ACMG-AMP guidelines, genetic testing, MEN1, missense variants, pathogenicity 
      classification, sequence variation
EDAT- 2019/03/15 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/03/15 06:00
PHST- 2018/06/15 00:00 [received]
PHST- 2019/03/07 00:00 [revised]
PHST- 2019/03/13 00:00 [accepted]
PHST- 2019/03/15 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/03/15 06:00 [entrez]
AID - 10.1002/humu.23746 [doi]
PST - ppublish
SO  - Hum Mutat. 2019 Jun;40(6):661-674. doi: 10.1002/humu.23746. Epub 2019 Mar 28.