Evidence map›Paper›PMID 39741318›Full record

ArticleGenome medicine2024

Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.

A Drackley, C Somerville, P Arnaud, L M Baudhuin, N Hanna, M L Kluge, K Kotzer, C Boileau, L Bronicki, B Callewaert and 21 more

Abstract readConsensus Statement
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

A DrackleyDepartment of Pathology & Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
C SomervilleGenetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
P ArnaudGenetics Department, Hôpital Bichat, Université Paris Cité, Paris, France.
L M BaudhuinDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
N HannaGenetics Department, Hôpital Bichat, Université Paris Cité, Paris, France.
M L KlugeDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
K KotzerDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
C BoileauGenetics Department, Hôpital Bichat, Université Paris Cité, Paris, France.
L BronickiGenetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
B CallewaertCentre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
A CecchiDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
H DietzMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
D GuoDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
S HarrisCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
O JarinovaGenetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
M LindsayCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
L LittleGenetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
B LoeysEuropean Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD and MSA Rare Disease, Working Group, Paris, France.
G MacCarrickMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J MeesterEuropean Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD and MSA Rare Disease, Working Group, Paris, France.
D MilewiczDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
T MorisakiIMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan.
H MorisakiIMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan.
D MurdockDepartment of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
M RenardCentre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
J RicherDepartment of Medical Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
L RobertDepartment of Cardiology, Guy's and St Thomas' Foundation Trust, London, UK.
M OuzounianDivision of Cardiac Surgery, University of Toronto, Toronto, ON, Canada.
L Van LaerEuropean Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD and MSA Rare Disease, Working Group, Paris, France.
J De Backer *European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD and MSA Rare Disease, Working Group, Paris, France.
L Muiño-Mosquera *European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD and MSA Rare Disease, Working Group, Paris, France. Laura.muinomosquera@uzgent.be.ORCID 0000-0002-3094-7807

Funding

The Clinical Genome Resource – Advancing genomic medicine through biocuration and expert assessment of genes and variants at scaleU24HG009650 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JONATHAN S BERG, Jessica Ezzell Hunter · 2021 to 2026
$30.0M
NHGRI NIH HHS U24 HG009650
6 · The paper itself

Abstract

backgroundIn 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) developed standardized variant curation guidelines for Mendelian disorders. Although these guidelines have been widely adopted, they are not gene- or disease-specific. To mitigate classification discrepancies, the Clinical Genome Resource FBN1 variant curation expert panel (VCEP) was established in 2018 to develop adaptations to the ACMG/AMP criteria for FBN1 in association with Marfan syndrome.

methodsThe specific recommendations were developed through literature review, surveys, online expert panel discussions, and pilot testing of a set of 60 different variants. Consensus among experts was considered reached if at least 75% of the members agreed with a given rule specification. The final set of rules received approval from the ClinGen Sequence Variant Interpretation Working Group.

resultsThe developed specifications introduce modifications to 14 of the 28 ACMG/AMP evidence criteria and deem 6 criteria non-applicable. Some of these specifications include refining the minor allele frequency thresholds, creating a FBN1-specific flowchart for PVS1, defining functional domains of the protein, developing a point-based system of counting probands and instances of de novo occurrences, recommending a points-based method of accounting for family segregation data, and clarifying the applicable functional assays that should be considered. To date, this VCEP has curated 120 variants which have been deposited to ClinVar with the 3-star review status.

conclusionsEstablishing specific adaptations for FBN1 has provided a framework to foster greater classification concordance among clinical laboratories, ultimately improving clinical care for patients with Marfan syndrome.

Indexed as

Fibrillin-1Genetic VariationMarfan SyndromeAdipokinesGenetic Predisposition to DiseaseGenome, HumanGenomicsHumansAdipokinesFBN1 protein, humanFibrillin-1ACMG-AMP guidelinesFBN1Marfan syndromeVariant curationVariant interpretation

Identifiers

PMID39741318
PMCPMC11686912

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.