ClinGen--the Clinical Genome Resource.

By H. Rehm, J. Berg, L. Brooks, Carlos D. Bustamante, James P. Evans, M. Landrum, D. Ledbetter, Donna R. Maglott, C. Martin, R. Nussbaum and 4 more. New England Journal of Medicine, 2015

1,269 citations recorded by the source corpus.

On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as “likely benign” by another laboratory that uses more recently derived population-frequency data. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant. An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death.

Subfields: Cardiology and Cardiovascular Medicine, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/30fc5297c5d0c28ee282b7b9ed52f4c5f3924720

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

In Genetics

In Molecular Biology

Citations in the corpus

Genenames.org: the HGNC resources in 2023 (2022, background): “In addition, the HGNC data section may include curator notes and/or links to gene groups curated by the HGNC. HGNC Symbol Reports also provide numerous useful external data links to biomedical resources such as NCBI Gene (5), Ensembl (6) UniProt (7), GeneCards (8), RNAcentral (9), UCSC genome browse”
The Encyclopedia of DNA elements (ENCODE): data portal update (2017, methodology): “The software is fully open source and has been adopted by the 4D-Nucleome Project (4DN, (15)) and Clinical Genome Resource (ClinGen, (16)) projects.”
2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. (2019, background): “genes in relation to specific disorders.(108) One of the first efforts in adapting the ACMG 2015 guidelines for variant interpretation in genes related to cardiogenetic disease has recently been”
Adaptation and Validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: Recommendations by ClinGen’s Inherited Cardiomyopathy Expert Panel (2018, neutral): “The historic lack of standardization is a major contributor for interpretation differences, which have been revealed by increased data sharing through ClinVar 1–3 .”
The DisGeNET knowledge platform for disease genomics: 2019 update (2019, background): “The GDAs and VDAs integrated in the DisGeNET database originate from over a dozen repositories, each one with a different focus, for example, databases that annotate clinically relevant variants (ClinVar) or genes (ClinGen, Genomics England Pan-Nucleic elApp, among others), or specialized in certain”
Evaluating drug targets through human loss-of-function genetic variation (2019, neutral): “%) for genes known to cause severe diseases of haploinsufficiency 18 (ClinGen Level 3).”
Settling the score: variant prioritization and Mendelian disease (2017, methodology): “However, it is clear that resources for these activities will eventually emerge from large projects such as the Genomics England 100,000 Genome Project (UK100K), the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme and the NHGRI Centers for Common Disease Genomics, which are each focused ”
Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples (2016, background): “org (46)), alongside large population databases representing diverse ethnic origins, preferably linked to phenotypic data.”