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1. AI-Enhanced Sensemaking: Exploring the Design of a Generative AI-Based Assistant to Support Genetic Professionals

Author

Mastrianni, Angela, Twede, Hope, Sarcevic, Aleksandra, Wander, Jeremiah, Austin-Tse, Christina, Saponas, Scott, Rehm, Heidi, Conard, Ashley Mae, and Hall, Amanda K.

Subjects
Computer Science - Human-Computer Interaction, Computer Science - Artificial Intelligence
Abstract

Generative AI has the potential to transform knowledge work, but further research is needed to understand how knowledge workers envision using and interacting with generative AI. We investigate the development of generative AI tools to support domain experts in knowledge work, examining task delegation and the design of human-AI interactions. Our research focused on designing a generative AI assistant to aid genetic professionals in analyzing whole genome sequences (WGS) and other clinical data for rare disease diagnosis. Through interviews with 17 genetics professionals, we identified current challenges in WGS analysis. We then conducted co-design sessions with six genetics professionals to determine tasks that could be supported by an AI assistant and considerations for designing interactions with the AI assistant. From our findings, we identified sensemaking as both a current challenge in WGS analysis and a process that could be supported by AI. We contribute an understanding of how domain experts envision interacting with generative AI in their knowledge work, a detailed empirical study of WGS analysis, and three design considerations for using generative AI to support domain experts in sensemaking during knowledge work. CCS CONCEPTS: Human-centered computing, Human-computer interaction, Empirical studies in HCI Additional Keywords and Phrases: whole genome sequencing, generative AI, large language models, knowledge work, sensemaking, co-design, rare disease Contact Author: Angela Mastrianni (This work was done during the author's internship at Microsoft Research) Ashley Mae Conard and Amanda K. Hall contributed equally, Comment: 22 pages, 8 figures, 1 table, 3 appendices

Published
2024

2. Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Author

Lemire, Gabrielle, Sanchis-Juan, Alba, Russell, Kathryn, Baxter, Samantha, Chao, Katherine, Singer-Berk, Moriel, Groopman, Emily, Wong, Isaac, England, Eleina, Goodrich, Julia, Pais, Lynn, Austin-Tse, Christina, DiTroia, Stephanie, OHeir, Emily, Ganesh, Vijay, Wojcik, Monica, Evangelista, Emily, Snow, Hana, Osei-Owusu, Ikeoluwa, Fu, Jack, Singh, Mugdha, Mostovoy, Yulia, Huang, Steve, Garimella, Kiran, Kirkham, Samantha, Neil, Jennifer, Shao, Diane, Walsh, Christopher, Argilli, Emanuela, Le, Carolyn, Sherr, Elliott, Gleeson, Joseph, Shril, Shirlee, Schneider, Ronen, Hildebrandt, Friedhelm, Sankaran, Vijay, Madden, Jill, Genetti, Casie, Beggs, Alan, Agrawal, Pankaj, Bujakowska, Kinga, Place, Emily, Pierce, Eric, Donkervoort, Sandra, Bönnemann, Carsten, Gallacher, Lyndon, Stark, Zornitza, Tan, Tiong, White, Susan, Töpf, Ana, Straub, Volker, Fleming, Mark, Pollak, Martin, Õunap, Katrin, Pajusalu, Sander, Donald, Kirsten, Bruwer, Zandre, Ravenscroft, Gianina, Laing, Nigel, MacArthur, Daniel, Rehm, Heidi, Talkowski, Michael, Brand, Harrison, and ODonnell-Luria, Anne

Subjects
CNV, GATK-gCNV, copy number variant, diagnostic yield, exome, variant classification, Humans, DNA Copy Number Variations, Rare Diseases, Exome, Male, Female, Exome Sequencing, Cohort Studies, Genetic Testing
Abstract

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

Published
2024

3. Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.

Author

Donkervoort, Sandra, Mohassel, Payam, OLeary, Melanie, Bonner, Devon, Hartley, Taila, Acquaye, Nicole, Brull, Astrid, Saporta, Mario, Dyment, David, Sampson, Jacinda, Pajusalu, Sander, Austin-Tse, Christina, Hurth, Kyle, Cohen, Julie, McWalter, Kirsty, Warman-Chardon, Jodi, Crunk, Amy, Foley, A, Mammen, Andrew, Wheeler, Matthew, ODonnell-Luria, Anne, Bönnemann, Carsten, and Mozaffar, Tahseen

Subjects
Adult, Humans, Muscular Diseases, Muscle, Skeletal, Actinin, Phenotype, Cardiomyopathies
Abstract

OBJECTIVE: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series. METHODS: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant. RESULTS: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing. INTERPRETATION: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease.

Published
2024

4. Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project

Author

Stenton, Sarah L., O’Leary, Melanie C., Lemire, Gabrielle, VanNoy, Grace E., DiTroia, Stephanie, Ganesh, Vijay S., Groopman, Emily, O’Heir, Emily, Mangilog, Brian, Osei-Owusu, Ikeoluwa, Pais, Lynn S., Serrano, Jillian, Singer-Berk, Moriel, Weisburd, Ben, Wilson, Michael W., Austin-Tse, Christina, Abdelhakim, Marwa, Althagafi, Azza, Babbi, Giulia, Bellazzi, Riccardo, Bovo, Samuele, Carta, Maria Giulia, Casadio, Rita, Coenen, Pieter-Jan, De Paoli, Federica, Floris, Matteo, Gajapathy, Manavalan, Hoehndorf, Robert, Jacobsen, Julius O. B., Joseph, Thomas, Kamandula, Akash, Katsonis, Panagiotis, Kint, Cyrielle, Lichtarge, Olivier, Limongelli, Ivan, Lu, Yulan, Magni, Paolo, Mamidi, Tarun Karthik Kumar, Martelli, Pier Luigi, Mulargia, Marta, Nicora, Giovanna, Nykamp, Keith, Pejaver, Vikas, Peng, Yisu, Pham, Thi Hong Cam, Podda, Maurizio S., Rao, Aditya, Rizzo, Ettore, Saipradeep, Vangala G., Savojardo, Castrense, Schols, Peter, Shen, Yang, Sivadasan, Naveen, Smedley, Damian, Soru, Dorian, Srinivasan, Rajgopal, Sun, Yuanfei, Sunderam, Uma, Tan, Wuwei, Tiwari, Naina, Wang, Xiao, Wang, Yaqiong, Williams, Amanda, Worthey, Elizabeth A., Yin, Rujie, You, Yuning, Zeiberg, Daniel, Zucca, Susanna, Bakolitsa, Constantina, Brenner, Steven E., Fullerton, Stephanie M., Radivojac, Predrag, Rehm, Heidi L., and O’Donnell-Luria, Anne

Published
2024
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5. Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies.

Author

Lowther, Chelsea, Valkanas, Elise, Giordano, Jessica, Wang, Harold, Currall, Benjamin, OKeefe, Kathryn, Pierce-Hoffman, Emma, Kurtas, Nehir, Whelan, Christopher, Hao, Stephanie, Weisburd, Ben, Jalili, Vahid, Fu, Jack, Wong, Isaac, Collins, Ryan, Zhao, Xuefang, Austin-Tse, Christina, Evangelista, Emily, Lemire, Gabrielle, Aggarwal, Vimla, Lucente, Diane, Gauthier, Laura, Tolonen, Charlotte, Sahakian, Nareh, Stevens, Christine, An, Joon-Yong, Dong, Shan, MacKenzie, Tippi, Devlin, Bernie, Gilmore, Kelly, Powell, Bradford, Brandt, Alicia, Vetrini, Francesco, DiVito, Michelle, MacArthur, Daniel, Hodge, Jennelle, ODonnell-Luria, Anne, Rehm, Heidi, Vora, Neeta, Levy, Brynn, Brand, Harrison, Wapner, Ronald, Talkowski, Michael, Norton, Mary, and Sanders, Stephan

Subjects
genome sequencing, karyotype, microarray, exome sequencing, structural variant, autism spectrum disorder, structural anomaly, prenatal, first-tier, diagnostic, Female, Pregnancy, Humans, Autism Spectrum Disorder, Pregnancy Trimester, First, Ultrasonography, Prenatal, Chromosome Mapping, Exome
Abstract

Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.

Published
2023

6. Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection

Author

Negi, Shloka, Stenton, Sarah L., Berger, Seth I., Canigiula, Paolo, McNulty, Brandy, Violich, Ivo, Gardner, Joshua, Hillaker, Todd, O’Rourke, Sara M., O’Leary, Melanie C., Carbonell, Elizabeth, Austin-Tse, Christina, Lemire, Gabrielle, Serrano, Jillian, Mangilog, Brian, VanNoy, Grace, Kolmogorov, Mikhail, Vilain, Eric, O’Donnell-Luria, Anne, Délot, Emmanuèle, Miga, Karen H., Monlong, Jean, and Paten, Benedict

Published
2025
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7. Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

Author

Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Carter, Jennefer, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Delot, Emmanuele, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garcia, Brandon, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Page, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Sousa, Rodrigo Guarischi, Gudmundsson, Sanna, Gulati, Ashima, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lee, Arthur, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James (Jim), Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Mastrorosa, Francesco Kumara, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Mendez, Hector Rodrigo, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Nguyen, Thuy-mi P., Nguyen, Jonathan, Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria`Sara, Ponce, Sarah, Porter, Elizabeth, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Evette, Scott, Stuart, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Kevin, Smith, Josh, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael (Mike), Tise, Christina, Tong, Catherine (Cat), Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Wei, Chia-Lin, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Chong, Jessica X., Berger, Seth I., Smith, Erica, Calame, Daniel G., Hawley, Megan H., Rivera-Munoz, E. Andres, Bamshad, Michael J., and Rehm, Heidi L.

Published
2024
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9. Monogenic and Polygenic Contributions to QTc Prolongation in the Population.

Author

Nauffal, Victor, Morrill, Valerie N, Jurgens, Sean J, Choi, Seung Hoan, Hall, Amelia W, Weng, Lu-Chen, Halford, Jennifer L, Austin-Tse, Christina, Haggerty, Christopher M, Harris, Stephanie L, Wong, Eugene K, Alonso, Alvaro, Arking, Dan E, Benjamin, Emelia J, Boerwinkle, Eric, Min, Yuan-I, Correa, Adolfo, Fornwalt, Brandon K, Heckbert, Susan R, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Kooperberg, Charles, Lin, Henry J, J F Loos, Ruth, Rice, Kenneth M, Gupta, Namrata, Blackwell, Thomas W, Mitchell, Braxton D, Morrison, Alanna C, Psaty, Bruce M, Post, Wendy S, Redline, Susan, Rehm, Heidi L, Rich, Stephen S, Rotter, Jerome I, Soliman, Elsayed Z, Sotoodehnia, Nona, Lunetta, Kathryn L, Ellinor, Patrick T, Lubitz, Steven A, and TOPMed Investigators

Subjects
National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Investigators, Humans, Long QT Syndrome, Electrocardiography, Heterozygote, Multifactorial Inheritance, Genome-Wide Association Study, Whole Genome Sequencing, QT interval, long QT syndrome, monogenic, polygenic, sudden cardiac death, Human Genome, Heart Disease, Prevention, Cardiovascular, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundRare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population.MethodsWe performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed.ResultsFifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS).ConclusionsQTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.

Published
2022

10. Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes

Author

Halford, Jennifer L, Morrill, Valerie N, Choi, Seung Hoan, Jurgens, Sean J, Melloni, Giorgio, Marston, Nicholas A, Weng, Lu-Chen, Nauffal, Victor, Hall, Amelia W, Gunn, Sophia, Austin-Tse, Christina A, Pirruccello, James P, Khurshid, Shaan, Rehm, Heidi L, Benjamin, Emelia J, Boerwinkle, Eric, Brody, Jennifer A, Correa, Adolfo, Fornwalt, Brandon K, Gupta, Namrata, Haggerty, Christopher M, Harris, Stephanie, Heckbert, Susan R, Hong, Charles C, Kooperberg, Charles, Lin, Henry J, Loos, Ruth JF, Mitchell, Braxton D, Morrison, Alanna C, Post, Wendy, Psaty, Bruce M, Redline, Susan, Rice, Kenneth M, Rich, Stephen S, Rotter, Jerome I, Schnatz, Peter F, Soliman, Elsayed Z, Sotoodehnia, Nona, Wong, Eugene K, Sabatine, Marc S, Ruff, Christian T, Lunetta, Kathryn L, Ellinor, Patrick T, and Lubitz, Steven A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Disease Susceptibility, Endophenotypes, Humans, Long QT Syndrome, Virulence, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P

Published
2022

11. Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing data sets

Author

Weisburd, Ben, Sharma, Rakshya, Pata, Villem, Reimand, Tiia, Ganesh, Vijay S., Austin-Tse, Christina, Osei-Owusu, Ikeoluwa, O’Heir, Emily, O’Leary, Melanie, Pais, Lynn, Stafki, Seth A., Daugherty, Audrey L., Folland, Chiara, Perić, Stojan, Fahmy, Nagia, Udd, Bjarne, Horakova, Magda, Łusakowska, Anna, Manoj, Rajanna, Nalini, Atchayaram, Karcagi, Veronika, Polavarapu, Kiran, Lochmüller, Hanns, Horvath, Rita, Bönnemann, Carsten G., Donkervoort, Sandra, Haliloğlu, Göknur, Herguner, Ozlem, Kang, Peter B., Ravenscroft, Gianina, Laing, Nigel, Scott, Hamish S., Töpf, Ana, Straub, Volker, Pajusalu, Sander, Õunap, Katrin, Tiao, Grace, Rehm, Heidi L., and O’Donnell-Luria, Anne

Published
2024
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12. Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Author

Choi, Seung Hoan, Jurgens, Sean J, Haggerty, Christopher M, Hall, Amelia W, Halford, Jennifer L, Morrill, Valerie N, Weng, Lu-Chen, Lagerman, Braxton, Mirshahi, Tooraj, Pettinger, Mary, Guo, Xiuqing, Lin, Henry J, Alonso, Alvaro, Soliman, Elsayed Z, Kornej, Jelena, Lin, Honghuang, Moscati, Arden, Nadkarni, Girish N, Brody, Jennifer A, Wiggins, Kerri L, Cade, Brian E, Lee, Jiwon, Austin-Tse, Christina, Blackwell, Tom, Chaffin, Mark D, Lee, Christina J-Y, Rehm, Heidi L, Roselli, Carolina, Regeneron Genetics Center, Redline, Susan, Mitchell, Braxton D, Sotoodehnia, Nona, Psaty, Bruce M, Heckbert, Susan R, Loos, Ruth JF, Vasan, Ramachandran S, Benjamin, Emelia J, Correa, Adolfo, Boerwinkle, Eric, Arking, Dan E, Rotter, Jerome I, Rich, Stephen S, Whitsel, Eric A, Perez, Marco, Kooperberg, Charles, Fornwalt, Brandon K, Lunetta, Kathryn L, Ellinor, Patrick T, Lubitz, Steven A, and NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

Subjects
Regeneron Genetics Center, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Humans, Long QT Syndrome, Death, Sudden, Cardiac, Genetic Predisposition to Disease, Electrocardiography, Heterozygote, Female, Male, Genetic Variation, Exome Sequencing, death, sudden, cardiac, epidemiology, genetics, genome, population, Clinical Research, Cardiovascular, Genetics, Heart Disease, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, death, sudden, cardiac
Abstract

BackgroundAlterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.MethodsUsing a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).ResultsWe found that rare variants associated with population-based electrocardiographic intervals identify established monogenic SCD genes (KCNQ1, KCNH2, and SCN5A), a controversial monogenic SCD gene (KCNE1), and novel genes (PAM and MFGE8) involved in cardiac conduction. Loss-of-function and pathogenic SCN5A variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (P=8.4×10-5). Similar variants in KCNQ1 and KCNH2 (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (P=4×10-25), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.ConclusionsOur findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.

Published
2021

13. Beyond the exome: What’s next in diagnostic testing for Mendelian conditions

Author

Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Bozkurt-Yozgatli, Tugce, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Délot, Emmanuèle, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fatih, Jawid, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Pagé, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Guarischi Sousa, Rodrigo, Gudmundsson, Sanna, Gulati, Ashima, Guo, Daniel, Hale, Walker, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Herman, Isabella, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kohler, Jennefer, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James, Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Kumara Mastrorosa, Francesco, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Rodrigo Mendez, Hector, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moussa, Hala Mohamed, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Neu, Matthew B., Nguyen, Jonathan, Nguyen, Thuy-mi P., Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria, Ponce, Sarah, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Stuart, Scott, Evette, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Josh, Smith, Kevin, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sundaram, Laksshman, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael, Tise, Christina, Tong, Catherine, Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Wong, Issac, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Wojcik, Monica H., Reuter, Chloe M., Duyzend, Michael H., Boone, Philip M., Groopman, Emily E., Délot, Emmanuèle C., Jain, Deepti, Starita, Lea M., Montgomery, Stephen B., Bamshad, Michael J., Chong, Jessica X., Wheeler, Matthew T., Berger, Seth I., and Sedlazeck, Fritz J.

Published
2023
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14. The Gene Curation Coalition: A global effort to harmonize gene–disease evidence resources

Author

DiStefano, Marina T., Goehringer, Scott, Babb, Lawrence, Alkuraya, Fowzan S., Amberger, Joanna, Amin, Mutaz, Austin-Tse, Christina, Balzotti, Marie, Berg, Jonathan S., Birney, Ewan, Bocchini, Carol, Bruford, Elspeth A., Coffey, Alison J., Collins, Heather, Cunningham, Fiona, Daugherty, Louise C., Einhorn, Yaron, Firth, Helen V., Fitzpatrick, David R., Foulger, Rebecca E., Goldstein, Jennifer, Hamosh, Ada, Hurles, Matthew R., Leigh, Sarah E., Leong, Ivone U.S., Maddirevula, Sateesh, Martin, Christa L., McDonagh, Ellen M., Olry, Annie, Puzriakova, Arina, Radtke, Kelly, Ramos, Erin M., Rath, Ana, Riggs, Erin Rooney, Roberts, Angharad M., Rodwell, Charlotte, Snow, Catherine, Stark, Zornitza, Tahiliani, Jackie, Tweedie, Susan, Ware, James S., Weller, Phillip, Williams, Eleanor, Wright, Caroline F., Yates, Thabo Michael, and Rehm, Heidi L.

Published
2022
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15. Centers for Mendelian Genomics: A decade of facilitating gene discovery

Author

Adams, Marcia, Aguet, François, Akay, Gulsen, Anderson, Peter, Antonescu, Corina, Arachchi, Harindra M., Atik, Mehmed M., Austin-Tse, Christina A., Babb, Larry, Bacus, Tamara J., Bahrambeigi, Vahid, Balasubramanian, Suganthi, Bayram, Yavuz, Beaudet, Arthur L., Beck, Christine R., Belmont, John W., Below, Jennifer E., Bilguvar, Kaya, Boehm, Corinne D., Boerwinkle, Eric, Boone, Philip M., Bowne, Sara J., Brand, Harrison, Buckingham, Kati J., Byrne, Alicia B., Calame, Daniel, Campbell, Ian M., Cao, Xiaolong, Carvalho, Claudia, Chander, Varuna, Chang, Jaime, Chao, Katherine R., Chinn, Ivan K., Clarke, Declan, Collins, Ryan L., Cummings, Beryl, Dardas, Zain, Dawood, Moez, Delano, Kayla, DiTroia, Stephanie P., Doddapaneni, Harshavardhan, Du, Haowei, Du, Renqian, Duan, Ruizhi, Eldomery, Mohammad, Eng, Christine M., England, Eleina, Evangelista, Emily, Everett, Selin, Fatih, Jawid, Felsenfeld, Adam, Francioli, Laurent C., Frazar, Christian D., Fu, Jack, Gamarra, Emmanuel, Gambin, Tomasz, Gan, Weiniu, Gandhi, Mira, Ganesh, Vijay S., Garimella, Kiran V., Gauthier, Laura D., Giroux, Danielle, Gonzaga-Jauregui, Claudia, Goodrich, Julia K., Gordon, William W., Griffith, Sean, Grochowski, Christopher M., Gu, Shen, Gudmundsson, Sanna, Hall, Stacey J., Hansen, Adam, Harel, Tamar, Harmanci, Arif O., Herman, Isabella, Hetrick, Kurt, Hijazi, Hadia, Horike-Pyne, Martha, Hsu, Elvin, Hu, Jianhong, Huang, Yongqing, Hurless, Jameson R., Jahl, Steve, Jarvik, Gail P., Jiang, Yunyun, Johanson, Eric, Jolly, Angad, Karaca, Ender, Khayat, Michael, Knight, James, Kolar, J. Thomas, Kumar, Sushant, Lalani, Seema, Laricchia, Kristen M., Larkin, Kathryn E., Leal, Suzanne M., Lemire, Gabrielle, Lewis, Richard A., Li, He, Ling, Hua, Lipson, Rachel B., Liu, Pengfei, Lovgren, Alysia Kern, López-Giráldez, Francesc, MacMillan, Melissa P., Mangilog, Brian E., Mano, Stacy, Marafi, Dana, Marosy, Beth, Marshall, Jamie L., Martin, Renan, Marvin, Colby T., Mawhinney, Michelle, McGee, Sean, McGoldrick, Daniel J., Mehaffey, Michelle, Mekonnen, Betselote, Meng, Xiaolu, Mitani, Tadahiro, Miyake, Christina Y., Mohr, David, Morris, Shaine, Mullen, Thomas E., Murdock, David R., Murugan, Mullai, Muzny, Donna M., Myers, Ben, Neira, Juanita, Nguyen, Kevin K., Nielsen, Patrick M., Nudelman, Natalie, O’Heir, Emily, O’Leary, Melanie C., Ongaco, Chrissie, Orange, Jordan, Osei-Owusu, Ikeoluwa A., Paine, Ingrid S., Pais, Lynn S., Paschall, Justin, Patterson, Karynne, Pehlivan, Davut, Pelle, Benjamin, Penney, Samantha, Perez de Acha Chavez, Jorge, Pierce-Hoffman, Emma, Poli, Cecilia M., Punetha, Jaya, Radhakrishnan, Aparna, Richardson, Matthew A., Rodrigues, Eliete, Roote, Gwendolin T., Rosenfeld, Jill A., Ryke, Erica L., Sabo, Aniko, Sanchez, Alice, Schrauwen, Isabelle, Scott, Daryl A., Sedlazeck, Fritz, Serrano, Jillian, Shaw, Chad A., Shelford, Tameka, Shively, Kathryn M., Singer-Berk, Moriel, Smith, Joshua D., Snow, Hana, Snyder, Grace, Solomonson, Matthew, Son, Rachel G., Song, Xiaofei, Stankiewicz, Pawel, Stephan, Taylorlyn, Sutton, V. Reid, Sveden, Abigail, Sánchez, Diana Cornejo, Tackett, Monica, Talkowski, Michael, Threlkeld, Machiko S., Tiao, Grace, Udler, Miriam S., Vail, Laura, Valivullah, Zaheer, Valkanas, Elise, VanNoy, Grace E., Wang, Qingbo S., Wang, Gao, Wang, Lu, Wangler, Michael F., Watts, Nicholas A., Weisburd, Ben, Weiss, Jeffrey M., Wheeler, Marsha M., White, Janson J., Williamson, Clara E., Wilson, Michael W., Wiszniewski, Wojciech, Withers, Marjorie A., Witmer, Dane, Witzgall, Lauren, Wohler, Elizabeth, Wojcik, Monica H., Wong, Isaac, Wood, Jordan C., Wu, Nan, Xing, Jinchuan, Yang, Yaping, Yi, Qian, Yuan, Bo, Zeiger, Jordan E., Zhang, Chaofan, Zhang, Peng, Zhang, Yan, Zhang, Xiaohong, Zhang, Yeting, Zhang, Shifa, Zoghbi, Huda, van den Veyver, Igna, Baxter, Samantha M., Posey, Jennifer E., Lake, Nicole J., Sobreira, Nara, Chong, Jessica X., Buyske, Steven, Blue, Elizabeth E., Chadwick, Lisa H., Coban-Akdemir, Zeynep H., Doheny, Kimberly F., Davis, Colleen P., Lek, Monkol, Wellington, Christopher, Jhangiani, Shalini N., Gerstein, Mark, Gibbs, Richard A., Lifton, Richard P., MacArthur, Daniel G., Matise, Tara C., Lupski, James R., Valle, David, Bamshad, Michael J., Hamosh, Ada, Mane, Shrikant, Nickerson, Deborah A., Rehm, Heidi L., and O’Donnell-Luria, Anne

Published
2022
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17. Publisher Correction: Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes

Author

Halford, Jennifer L., Morrill, Valerie N., Choi, Seung Hoan, Jurgens, Sean J., Melloni, Giorgio, Marston, Nicholas A., Weng, Lu-Chen, Nauffal, Victor, Hall, Amelia W., Gunn, Sophia, Austin-Tse, Christina A., Pirruccello, James P., Khurshid, Shaan, Rehm, Heidi L., Benjamin, Emelia J., Boerwinkle, Eric, Brody, Jennifer A., Correa, Adolfo, Fornwalt, Brandon K., Gupta, Namrata, Haggerty, Christopher M., Harris, Stephanie, Heckbert, Susan R., Hong, Charles C., Kooperberg, Charles, Lin, Henry J., Loos, Ruth J. F., Mitchell, Braxton D., Morrison, Alanna C., Post, Wendy, Psaty, Bruce M., Redline, Susan, Rice, Kenneth M., Rich, Stephen S., Rotter, Jerome I., Schnatz, Peter F., Soliman, Elsayed Z., Sotoodehnia, Nona, Wong, Eugene K., Sabatine, Marc S., Ruff, Christian T., Lunetta, Kathryn L., Ellinor, Patrick T., and Lubitz, Steven A.

Published
2022
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18. Best practices for the interpretation and reporting of clinical whole genome sequencing

Author

Austin-Tse, Christina A., Jobanputra, Vaidehi, Perry, Denise L., Bick, David, Taft, Ryan J., Venner, Eric, Gibbs, Richard A., Young, Ted, Barnett, Sarah, Belmont, John W., Boczek, Nicole, Chowdhury, Shimul, Ellsworth, Katarzyna A., Guha, Saurav, Kulkarni, Shashikant, Marcou, Cherisse, Meng, Linyan, Murdock, David R., Rehman, Atteeq U., Spiteri, Elizabeth, Thomas-Wilson, Amanda, Kearney, Hutton M., and Rehm, Heidi L.

Published
2022
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19. Genome Sequencing for Diagnosing Rare Diseases

Author

Wojcik, Monica H., primary, Lemire, Gabrielle, additional, Berger, Eva, additional, Zaki, Maha S., additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Susan M., additional, Weisburd, Ben, additional, Wieczorek, Dagmar, additional, Waddell, Leigh B., additional, Verboon, Jeffrey M., additional, VanNoy, Grace E., additional, Töpf, Ana, additional, Tan, Tiong Yang, additional, Syrbe, Steffen, additional, Strehlow, Vincent, additional, Straub, Volker, additional, Stenton, Sarah L., additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G., additional, Schneider, Ronen, additional, Sankaran, Vijay G., additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A., additional, Reinson, Karit, additional, Ravenscroft, Gianina, additional, Radtke, Maximilian, additional, Popp, Denny, additional, Polster, Tilman, additional, Platzer, Konrad, additional, Pierce, Eric A., additional, Place, Emily M., additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Õunap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Opperman, Henry, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, O’Leary, Melanie, additional, O’Heir, Emily, additional, Morel, Chantal F., additional, Merkenschlager, Andreas, additional, Marchant, Rhett G., additional, Mangilog, Brian E., additional, Madden, Jill A., additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P., additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Hentschel, Julia, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G., additional, Ghaoui, Roula, additional, Genetti, Casie A., additional, Gburek-Augustat, Janina, additional, Gazda, Hanna T., additional, Ganesh, Vijay S., additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack M., additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T., additional, Chung, Wendy K., additional, Christodoulou, John, additional, Chao, Katherine R., additional, Cato, Liam D., additional, Bujakowska, Kinga M., additional, Bryen, Samantha J., additional, Brand, Harrison, additional, Bönnemann, Carsten G., additional, Beggs, Alan H., additional, Baxter, Samantha M., additional, Bartolomaeus, Tobias, additional, Agrawal, Pankaj B., additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Abou Jamra, Rami, additional, Rehm, Heidi L., additional, and O’Donnell-Luria, Anne, additional

Published
2024
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20. Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test

Author

Brockman, Deanna G., Austin-Tse, Christina A., Pelletier, Renée C., Harley, Caroline, Patterson, Candace, Head, Holly, Leonard, Courtney Elizabeth, O’Brien, Kimberly, Mahanta, Lisa M., Lebo, Matthew S., Lu, Christine Y., Natarajan, Pradeep, Khera, Amit V., Aragam, Krishna G., Kathiresan, Sekar, Rehm, Heidi L., and Udler, Miriam S.

Published
2021
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21. Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel

Author

Morales, Ana, Ing, Alexander, Antolik, Christian, Austin-Tse, Christina, Baudhuin, Linnea M., Bronicki, Lucas, Cirino, Allison, Hawley, Megan H., Fietz, Michael, Garcia, John, Ho, Carolyn, Ingles, Jodie, Jarinova, Olga, Johnston, Tami, Kelly, Melissa A., Kurtz, C. Lisa, Lebo, Matt, Macaya, Daniela, Mahanta, Lisa, Maleszewski, Joseph, Manrai, Arjun K., Murray, Mitzi, Richard, Gabriele, Semsarian, Chris, Thomson, Kate L., Winder, Tom, Ware, James S., Hershberger, Ray E., Funke, Birgit H., and Vatta, Matteo

Published
2021
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22. Protein‐extending ACTN2 frameshift variants cause variable myopathy phenotypes by protein aggregation.

Author

Ranta‐aho, Johanna, Felice, Kevin J., Jonson, Per Harald, Sarparanta, Jaakko, Yvorel, Cédric, Harzallah, Ines, Touraine, Renaud, Pais, Lynn, Austin‐Tse, Christina A., Ganesh, Vijay S., O'Leary, Melanie C., Rehm, Heidi L., Hehir, Michael K., Subramony, Sub, Wu, Qian, Udd, Bjarne, and Savarese, Marco

Subjects
MISSENSE mutation, GENETIC disorders, SARCOMERES, PHENOTYPES, CONNECTIN
Abstract

Objective: The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha‐actinin‐2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha‐actinin‐2 is to link actin and titin to the sarcomere Z‐disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype–phenotype correlations in ACTN2‐related diseases, actininopathies, persists. Methods: Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype–phenotype correlations of actininopathies using clinical data from several patients carrying these variants. Results: The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha‐actinin‐2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha‐actinin‐2 aggregates. Interpretation: The results suggest that alpha‐actinin‐2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein‐extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Detecting missed diagnoses of spinal muscular atrophy in genome, exome, and panel sequencing datasets

Author

Weisburd, Ben, primary, Sharma, Rakshya, additional, Pata, Villem, additional, Reimand, Tiia, additional, Ganesh, Vijay S., additional, Austin-Tse, Christina, additional, Osei-Owusu, Ikeoluwa, additional, O'Heir, Emily, additional, O'Leary, Melanie, additional, Pais, Lynn, additional, Stafki, Seth A., additional, Daugherty, Audrey L., additional, Bonnemann, Carsten G., additional, Donkervoort, Sandra, additional, Haliloglu, Goknur, additional, Kang, Peter B., additional, Ravenscroft, Gianina, additional, Laing, Nigel, additional, Scott, Hamish S., additional, Topf, Ana, additional, Straub, Volker, additional, Pajusalu, Sander, additional, Ounap, Katrin, additional, Tiao, Grace, additional, Rehm, Heidi L., additional, and O'Donnell-Luria, Anne, additional

Published
2024
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24. RareACTN2Frameshift Variants Resulting in Protein Extension Cause Distal Myopathy and Hypertrophic Cardiomyopathy through Protein Aggregation

Author

Ranta-aho, Johanna, primary, Felice, Kevin J., additional, Jonson, Per Harald, additional, Sarparanta, Jaakko, additional, Palmio, Johanna, additional, Tasca, Giorgio, additional, Sabatelli, Mario, additional, Yvorel, Cédric, additional, Harzallah, Ines, additional, Touraine, Renaud, additional, Pais, Lynn, additional, Austin-Tse, Christina A., additional, Ganesh, Vijay, additional, O’Leary, Melanie C., additional, Rehm, Heidi L., additional, Hehir, Michael K., additional, Subramony, Sub, additional, Wu, Qian, additional, Udd, Bjarne, additional, and Savarese, Marco, additional

Published
2024
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25. Contributors

Author

Alves, Ana Catarina, primary, Austin-Tse, Christina Anne, additional, Bourbon, Mafalda, additional, Carvalho, Marcelo A., additional, Ceyhan-Birsoy, Ozge, additional, Charames, George S., additional, Chora, Joana Rita, additional, Colombo, Mara, additional, Cruz, Xavier de la, additional, den Dunnen, Johan T., additional, de Wind, Niels, additional, Diez, Orland, additional, Elias, Anna B.R., additional, Evans, D Gareth, additional, Feliubadaló, Lidia, additional, Fernandes, Vanessa C., additional, Fokkema, Ivo F.A.C., additional, Fortuno, Cristina, additional, Garrett, Alice, additional, Gasparini, Paolo, additional, Girotto, Giorgia, additional, González-Neira, Anna, additional, Gripp, Karen W., additional, Gutiérrez-Enríquez, Sara, additional, Harrison, Steven M., additional, Hoya, Miguel de la, additional, Ingles, Jodie, additional, Johnson, Renee, additional, Lerner-Ellis, Jordan, additional, Levy, Harvey, additional, Lázaro, Conxi, additional, Mason-Suares, Heather, additional, Medeiros, Ana Margarida, additional, Mester, Jessica L., additional, Moles-Fernández, Alejandro, additional, Monteiro, Alvaro N.A., additional, Morgan, Anna, additional, Nepomuceno, Thales C., additional, Núñez-Torres, Rocío, additional, Özkan, Selen, additional, Padilla, Natàlia, additional, Parsons, Michael T., additional, Pesaran, Tina F., additional, Pineda, Marta, additional, Radice, Paolo, additional, Rajabi, Farrah, additional, Richardson, Ebony, additional, Sabatini, Peter, additional, Sacharow, Stephanie, additional, Spurdle, Amanda, additional, Thompson, Bryony A., additional, Tudini, Emma, additional, Turnbull, Clare, additional, Vincent, Lisa M., additional, Walsh, Michael F., additional, and Watkins, Nicholas, additional

Published
2021
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28. Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

Author

Lemire, Gabrielle, primary, Sanchis-Juan, Alba, additional, Russell, Kathryn, additional, Baxter, Samantha, additional, Chao, Katherine R., additional, Singer-Berk, Moriel, additional, Groopman, Emily, additional, Wong, Isaac, additional, England, Eleina, additional, Goodrich, Julia, additional, Pais, Lynn, additional, Austin-Tse, Christina, additional, DiTroia, Stephanie, additional, O’Heir, Emily, additional, Ganesh, Vijay S., additional, Wojcik, Monica H., additional, Evangelista, Emily, additional, Snow, Hana, additional, Osei-Owusu, Ikeoluwa, additional, Fu, Jack, additional, Singh, Mugdha, additional, Mostovoy, Yulia, additional, Huang, Steve, additional, Garimella, Kiran, additional, Kirkham, Samantha L., additional, Neil, Jennifer E., additional, Shao, Diane D., additional, Walsh, Christopher A., additional, Argili, Emanuela, additional, Le, Carolyn, additional, Sherr, Elliott H., additional, Gleeson, Joseph, additional, Shril, Shirlee, additional, Schneider, Ronen, additional, Hildebrandt, Friedhelm, additional, Sankaran, Vijay G., additional, Madden, Jill A., additional, Genetti, Casie A., additional, Beggs, Alan H., additional, Agrawal, Pankaj B., additional, Bujakowska, Kinga M., additional, Place, Emily, additional, Pierce, Eric A., additional, Donkervoort, Sandra, additional, Bönnemann, Carsten G., additional, Gallacher, Lyndon, additional, Stark, Zornitza, additional, Tan, Tiong, additional, White, Susan M., additional, Töpf, Ana, additional, Straub, Volker, additional, Fleming, Mark D., additional, Pollak, Martin R., additional, Õunap, Katrin, additional, Pajusalu, Sander, additional, Donald, Kirsten A., additional, Bruwer, Zandre, additional, Ravenscroft, Gianina, additional, Laing, Nigel G., additional, MacArthur, Daniel G., additional, Rehm, Heidi L., additional, Talkowski, Michael E., additional, Brand, Harrison, additional, and O’Donnell-Luria, Anne, additional

Published
2023
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29. Electronic health record phenotype in subjects with genetic variants associated with arrhythmogenic right ventricular cardiomyopathy: a study of 30,716 subjects with exome sequencing

Author

Haggerty, Christopher M, James, Cynthia A, Calkins, Hugh, Tichnell, Crystal, Leader, Joseph B, Hartzel, Dustin N, Nevius, Christopher D, Pendergrass, Sarah A, Person, Thomas N, Schwartz, Marci, Ritchie, Marylyn D, Carey, David J, Ledbetter, David H, Williams, Marc S, Dewey, Frederick E, Lopez, Alexander, Penn, John, Overton, John D, Reid, Jeffrey G, Lebo, Matthew, Mason-Suares, Heather, Austin-Tse, Christina, Rehm, Heidi L, Delisle, Brian P, Makowski, Daniel J, Mehra, Vishal C, Murray, Michael F, and Fornwalt, Brandon K

Published
2017
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30. Abstract 14629: Rare Variants for Electrocardiographic Traits Identify Arrhythmia Susceptibility Genes

Author

Jurgens, Sean J, Choi, Seung Hoan, Haggerty, Christopher M, Hall, Amelia W, Halford, Jennifer, Morrill, Valerie, Weng, Lu Chen, Lagerman, Braxton, Mirshahi, Tooraj, Pettinger, Mary, Guo, Xiuqing, Kornej, Jelena, Lin, Honghuang, Moscati, Arden, Nadkarni, Girish, Brody, Jennifer, Wiggins, Kerri, Cade, Brian E, Lee, Jiwon, Austin-Tse, Christina, Blackwell, Tom, Chaffin, Mark, Lee, Christina J, Rehm, Heidi, Redline, Susan, Mitchell, Braxton D, Sotoodehnia, Nona, Psaty, Bruce M, Heckbert, Susan R, Loos, Ruth J, Vasan, Ramachandran S, Benjamin, Emelia J, Correa, Adolfo, Boerwinkle, Eric, Arking, Dan E, Rotter, Jerome I, Rich, Stephen, Whitsel, Eric A, Perez, Marco V, Kooperberg, Charles, Fornwalt, Brandon, Lunetta, Kathryn, Ellinor, Patrick T, and Lubitz, Steven A

Published
2020
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31. Identification of ade novomutation inTLK1associated with a neurodevelopmental disorder and immunodeficiency

Author

Villamor-Payà, Marina, primary, Sanchiz-Calvo, María, additional, Smak, Jordann, additional, Pais, Lynn, additional, Sud, Malika, additional, Shankavaram, Uma, additional, Lovgren, Alysia Kern, additional, Austin-Tse, Christina, additional, Ganesh, Vijay S, additional, Gay, Marina, additional, Vilaseca, Marta, additional, Arauz-Garofalo, Gianluca, additional, Palenzuela, Lluís, additional, VanNoy, Grace, additional, O’Donnell-Luria, Anne, additional, and Stracker, Travis H., additional

Published
2023
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32. Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

Author

Wojcik, Monica H, primary, Lemire, Gabrielle, additional, Zaki, Maha S, additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Sue, additional, Weisburd, Ben, additional, Waddell, Leigh B, additional, Verboon, Jeffrey M, additional, VanNoy, Grace E, additional, Topf, Ana, additional, Tan, Tiong Yang, additional, Straub, Volker, additional, Stenton, Sarah L, additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G, additional, Schneider, Ronen, additional, Sankaran, Vijay G, additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A, additional, Reinson, Karit, additional, Ravenscroft, Gina, additional, Pierce, Eric A, additional, Place, Emily M, additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Ounap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, OLeary, Melanie, additional, OHeir, Emily, additional, Morel, Chantal, additional, Marchant, Rhett G, additional, Mangilog, Brian E, additional, Madden, Jill A, additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P, additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G, additional, Ghaoui, Roula, additional, Genetti, Casie A, additional, Gazda, Hanna, additional, Ganesh, Vijay S, additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack, additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T, additional, Chung, Wendy K, additional, Christodoulou, John, additional, Chao, Katherine R, additional, Cato, Liam D, additional, Bujakowska, Kinga M, additional, Bryen, Samantha J, additional, Brand, Harrison, additional, Bonnemann, Carsten, additional, Beggs, Alan H, additional, Baxter, Samantha M, additional, Agrawal, Pankaj B, additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Rehm, Heidi L, additional, and ODonnell-Luria, Anne, additional

Published
2023
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33. Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project

Author

Stenton, Sarah L., primary, O’Leary, Melanie, additional, Lemire, Gabrielle, additional, VanNoy, Grace E., additional, DiTroia, Stephanie, additional, Ganesh, Vijay S., additional, Groopman, Emily, additional, O’Heir, Emily, additional, Mangilog, Brian, additional, Osei-Owusu, Ikeoluwa, additional, Pais, Lynn S., additional, Serrano, Jillian, additional, Singer-Berk, Moriel, additional, Weisburd, Ben, additional, Wilson, Michael, additional, Austin-Tse, Christina, additional, Abdelhakim, Marwa, additional, Althagafi, Azza, additional, Babbi, Giulia, additional, Bellazzi, Riccardo, additional, Bovo, Samuele, additional, Carta, Maria Giulia, additional, Casadio, Rita, additional, Coenen, Pieter-Jan, additional, De Paoli, Federica, additional, Floris, Matteo, additional, Gajapathy, Manavalan, additional, Hoehndorf, Robert, additional, Jacobsen, Julius O.B., additional, Joseph, Thomas, additional, Kamandula, Akash, additional, Katsonis, Panagiotis, additional, Kint, Cyrielle, additional, Lichtarge, Olivier, additional, Limongelli, Ivan, additional, Lu, Yulan, additional, Magni, Paolo, additional, Mamidi, Tarun Karthik Kumar, additional, Martelli, Pier Luigi, additional, Mulargia, Marta, additional, Nicora, Giovanna, additional, Nykamp, Keith, additional, Pejaver, Vikas, additional, Peng, Yisu, additional, Pham, Thi Hong Cam, additional, Podda, Maurizio S., additional, Rao, Aditya, additional, Rizzo, Ettore, additional, Saipradeep, Vangala G, additional, Savojardo, Castrense, additional, Schols, Peter, additional, Shen, Yang, additional, Sivadasan, Naveen, additional, Smedley, Damian, additional, Soru, Dorian, additional, Srinivasan, Rajgopal, additional, Sun, Yuanfei, additional, Sunderam, Uma, additional, Tan, Wuwei, additional, Tiwari, Naina, additional, Wang, Xiao, additional, Wang, Yaqiong, additional, Williams, Amanda, additional, Worthey, Elizabeth A., additional, Yin, Rujie, additional, You, Yuning, additional, Zeiberg, Daniel, additional, Zucca, Susanna, additional, Bakolitsa, Constantina, additional, Brenner, Steven E., additional, Fullerton, Stephanie M, additional, Radivojac, Predrag, additional, Rehm, Heidi L., additional, and O’Donnell-Luria, Anne, additional

Published
2023
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34. P575: The Rare Genomes Project: Improving access to genomic sequencing and identifying causes of rare disease*

Author

Austin-Tse, Christina, DiTroia, Stephanie, O'Leary, Melanie, VanNoy, Grace, Mangilog, Brian, Shah, Gulalai, Martinez, Eva, Serrano, Jillian, Pais, Lynn, O'Heir, Emily, Osei-Owusu, Ikeoluwa, Lemire, Gabrielle, Ganesh, Vijay, Stenton, Sarah, Amin, Mutaz, Socarras, Kayla, Singh, Mugdha, Hall, Stacey, Larsson, Katie, Singer-Berk, Moriel, Marten, Daniel, Wilson, Michael, Snow, Hana, Blankenmeister, Benjamin, Ma, Jialan, Weisburd, Ben, Sanchis-Juan, Alba, Brand, Harrison, Groopman, Emily, Lovgren, Alysia, Williamson, Clara, Hollyer, Marissa, England, Eleina, Seaby, Eleanor, Chao, Katherine, Goodrich, Julia, Baxter, Samantha, MacArthur, Daniel, Talkowski, Michael, Wojcik, Monica, O'Donnell-Luria, Anne, and Rehm, Heidi

Published
2024
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35. P570: Generating a framework for curating mechanism of disease in monogenic conditions: A consensus effort of the Gene Curation Coalition*

Author

DiStefano, Marina, Alkuraya, Fowzan, Amberger, Joanna, Austin-Tse, Christina, Austine, Ola, Balzotti, Marie, Berg, Jonathan, Bruford, Elspeth, Byrne, Alicia, Cibrian-Uhalte, Elena, Coffey, Alison, Firth, Helen, Hamosh, Ada, Hunt, Sarah, Klein, Teri, Kurtz, Catherine, Leigh, Sarah, Leong, Ivone, Lucano, Caterina, Maddirevula, Sateesh, O'Neill, Audrey, Puzriakova, Arina, Rath, Ana, Roberts, Angharad, Radtke, Kelly, Ramos, Erin, Riggs, Erin, Rodwell, Charlotte, Taylor, Julie, Sangkuhl, Katrin, Snow, Catherine, Stark, Zornitza, Ware, James, Wayburn, Bess, Weller, Phillip, and Rehm, Heidi

Published
2024
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37. JAK inhibition in a patient with a STAT1 gain-of-function variant reveals STAT1 dysregulation as a common feature of aplastic anemia

Author

Massachusetts Institute of Technology. Department of Biology, Rosenberg, Jacob M, Peters, Joshua M, Hughes, Travis, Lareau, Caleb A, Ludwig, Leif S, Massoth, Lucas R, Austin-Tse, Christina, Rehm, Heidi L, Bryson, Bryan, Chen, Yi-Bin, Regev, Aviv, Shalek, Alex K, Fortune, Sarah M, Sykes, David B, Massachusetts Institute of Technology. Department of Biology, Rosenberg, Jacob M, Peters, Joshua M, Hughes, Travis, Lareau, Caleb A, Ludwig, Leif S, Massoth, Lucas R, Austin-Tse, Christina, Rehm, Heidi L, Bryson, Bryan, Chen, Yi-Bin, Regev, Aviv, Shalek, Alex K, Fortune, Sarah M, and Sykes, David B

Published
2023

38. Phenotype and genetic analysis of data collected within the first year of NeuroDev

Author

Kipkemoi, Patricia, Kim, Heesu Ally, Christ, Bjorn, O’Heir, Emily, Allen, Jake, Austin-Tse, Christina, Baxter, Samantha, Brand, Harrison, Bryant, Sam, Buser, Nick, de Menil, Victoria, Eastman, Emma, Murugasen, Serini, Galvin, Alice, Kombe, Martha, Ngombo, Alfred, Mkubwa, Beatrice, Mwangi, Paul, Kipkoech, Collins, Lovgren, Alysia, MacArthur, Daniel G., Melly, Brigitte, Mwangasha, Katini, Martin, Alicia, Nkambule, Lethukuthula L., Sanchis-Juan, Alba, Singer-Berk, Moriel, Talkowski, Michael E., VanNoy, Grace, van der Merwe, Celia, Newton, Charles, O’Donnell-Luria, Anne, Abubakar, Amina, Donald, Kirsten A., and Robinson, Elise B.

Published
2023
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39. P523: The NeuroDev Study: Genetic characterization of neurodevelopmental disorders in African populations

Author

O'Heir, Emily, primary, Kipkemoi, Patricia, additional, Kim, Heesu Ally, additional, Christ, Bjorn, additional, Eastman, Emma, additional, van der Merwe, Celia, additional, Galvin, Alice, additional, Allen, Jake, additional, de Menil, Victoria, additional, Lovgren, Alysia, additional, Austin-Tse, Christina, additional, Abubakar, Amina, additional, Newton, Charles, additional, Donald, Kirsten, additional, O'Donnell-Luria, Anne, additional, and Robinson, Elise, additional

Published
2023
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40. P451: The Gene Curation Coalition works to resolve discrepancies in gene-disease validity assertions

Author

DiStefano, Marina, primary, Amberger, Joanna, additional, Austin-Tse, Christina, additional, Balzotti, Marie, additional, Amin, Mutaz, additional, Berg, Jonathan, additional, Bocchini, Carol, additional, Bruford, Elspeth, additional, Alkuraya, Fowzan, additional, Coffey, Alison, additional, Collins, Heather, additional, Cunningham, Fiona, additional, Firth, Helen, additional, Fitzpatrick, David, additional, Einhorn, Yaron, additional, Goldstein, Jennifer, additional, Hamosh, Ada, additional, Leigh, Sarah, additional, Leong, Ivone, additional, Martin, Christa, additional, McDonagh, Ellen, additional, Puzriakova, Arina, additional, Rath, Ana, additional, Roberts, Angharad, additional, Radtke, Kelly, additional, Ramos, Erin, additional, Riggs, Erin, additional, Rodwell, Charlotte, additional, Sangkuhl, Katrin, additional, Snow, Catherine, additional, Stark, Zornitza, additional, Tahiliani, Jackie, additional, Ware, James, additional, Williams, Eleanor, additional, Wright, Caroline, additional, Yates, Michael, additional, Weller, Phillip, additional, and Rehm, Heidi, additional

Published
2023
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42. Erratum: Publisher Correction: Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes (Nature communications (2022) 13 1 (5106))

Author

Halford, Jennifer L., Morrill, Valerie N., Choi, Seung Hoan, Jurgens, Sean J., Melloni, Giorgio, Marston, Nicholas A., Weng, Lu-Chen, Nauffal, Victor, Hall, Amelia W., Gunn, Sophia, Austin-Tse, Christina A., Pirruccello, James P., Khurshid, Shaan, Rehm, Heidi L., Benjamin, Emelia J., Boerwinkle, Eric, Brody, Jennifer A., Correa, Adolfo, Fornwalt, Brandon K., Gupta, Namrata, Haggerty, Christopher M., Harris, Stephanie, Heckbert, Susan R., Hong, Charles C., Kooperberg, Charles, Lin, Henry J., Loos, Ruth J. F., Mitchell, Braxton D., Morrison, Alanna C., Post, Wendy, Psaty, Bruce M., Redline, Susan, Rice, Kenneth M., Rich, Stephen S., Rotter, Jerome I., Schnatz, Peter F., Soliman, Elsayed Z., Sotoodehnia, Nona, Wong, Eugene K., Sabatine, Marc S., Ruff, Christian T., Lunetta, Kathryn L., Ellinor, Patrick T., Lubitz, Steven A., Cardiology, Graduate School, and ACS - Heart failure & arrhythmias

Published
2022

43. Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

Author

Austin-Tse, Christina, Halbritter, Jan, Zariwala, Maimoona A., Gilberti, Renée M., Gee, Heon Yung, Hellman, Nathan, Pathak, Narendra, Liu, Yan, Panizzi, Jennifer R., Patel-King, Ramila S., Tritschler, Douglas, Bower, Raqual, O’Toole, Eileen, Porath, Jonathan D., Hurd, Toby W., Chaki, Moumita, Diaz, Katrina A., Kohl, Stefan, Lovric, Svjetlana, Hwang, Daw-Yang, Braun, Daniela A., Schueler, Markus, Airik, Rannar, Otto, Edgar A., Leigh, Margaret W., Noone, Peadar G., Carson, Johnny L., Davis, Stephanie D., Pittman, Jessica E., Ferkol, Thomas W., Atkinson, Jeffry J., Olivier, Kenneth N., Sagel, Scott D., Dell, Sharon D., Rosenfeld, Margaret, Milla, Carlos E., Loges, Niki T., Omran, Heymut, Porter, Mary E., King, Stephen M., Knowles, Michael R., Drummond, Iain A., and Hildebrandt, Friedhelm

Published
2013
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44. Centers for Mendelian Genomics: A decade of facilitating gene discovery

Author

Baxter, Samantha M., primary, Posey, Jennifer E., additional, Lake, Nicole J., additional, Sobreira, Nara, additional, Chong, Jessica X., additional, Buyske, Steven, additional, Blue, Elizabeth E., additional, Chadwick, Lisa H., additional, Coban-Akdemir, Zeynep H., additional, Doheny, Kimberly F., additional, Davis, Colleen P., additional, Lek, Monkol, additional, Wellington, Christopher, additional, Jhangiani, Shalini N., additional, Gerstein, Mark, additional, Gibbs, Richard A., additional, Lifton, Richard P., additional, MacArthur, Daniel G., additional, Matise, Tara C., additional, Lupski, James R., additional, Valle, David, additional, Bamshad, Michael J., additional, Hamosh, Ada, additional, Mane, Shrikant, additional, Nickerson, Deborah A., additional, Rehm, Heidi L., additional, O’Donnell-Luria, Anne, additional, Adams, Marcia, additional, Aguet, François, additional, Akay, Gulsen, additional, Anderson, Peter, additional, Antonescu, Corina, additional, Arachchi, Harindra M., additional, Atik, Mehmed M., additional, Austin-Tse, Christina A., additional, Babb, Larry, additional, Bacus, Tamara J., additional, Bahrambeigi, Vahid, additional, Balasubramanian, Suganthi, additional, Bayram, Yavuz, additional, Beaudet, Arthur L., additional, Beck, Christine R., additional, Belmont, John W., additional, Below, Jennifer E., additional, Bilguvar, Kaya, additional, Boehm, Corinne D., additional, Boerwinkle, Eric, additional, Boone, Philip M., additional, Bowne, Sara J., additional, Brand, Harrison, additional, Buckingham, Kati J., additional, Byrne, Alicia B., additional, Calame, Daniel, additional, Campbell, Ian M., additional, Cao, Xiaolong, additional, Carvalho, Claudia, additional, Chander, Varuna, additional, Chang, Jaime, additional, Chao, Katherine R., additional, Chinn, Ivan K., additional, Clarke, Declan, additional, Collins, Ryan L., additional, Cummings, Beryl, additional, Dardas, Zain, additional, Dawood, Moez, additional, Delano, Kayla, additional, DiTroia, Stephanie P., additional, Doddapaneni, Harshavardhan, additional, Du, Haowei, additional, Du, Renqian, additional, Duan, Ruizhi, additional, Eldomery, Mohammad, additional, Eng, Christine M., additional, England, Eleina, additional, Evangelista, Emily, additional, Everett, Selin, additional, Fatih, Jawid, additional, Felsenfeld, Adam, additional, Francioli, Laurent C., additional, Frazar, Christian D., additional, Fu, Jack, additional, Gamarra, Emmanuel, additional, Gambin, Tomasz, additional, Gan, Weiniu, additional, Gandhi, Mira, additional, Ganesh, Vijay S., additional, Garimella, Kiran V., additional, Gauthier, Laura D., additional, Giroux, Danielle, additional, Gonzaga-Jauregui, Claudia, additional, Goodrich, Julia K., additional, Gordon, William W., additional, Griffith, Sean, additional, Grochowski, Christopher M., additional, Gu, Shen, additional, Gudmundsson, Sanna, additional, Hall, Stacey J., additional, Hansen, Adam, additional, Harel, Tamar, additional, Harmanci, Arif O., additional, Herman, Isabella, additional, Hetrick, Kurt, additional, Hijazi, Hadia, additional, Horike-Pyne, Martha, additional, Hsu, Elvin, additional, Hu, Jianhong, additional, Huang, Yongqing, additional, Hurless, Jameson R., additional, Jahl, Steve, additional, Jarvik, Gail P., additional, Jiang, Yunyun, additional, Johanson, Eric, additional, Jolly, Angad, additional, Karaca, Ender, additional, Khayat, Michael, additional, Knight, James, additional, Kolar, J. Thomas, additional, Kumar, Sushant, additional, Lalani, Seema, additional, Laricchia, Kristen M., additional, Larkin, Kathryn E., additional, Leal, Suzanne M., additional, Lemire, Gabrielle, additional, Lewis, Richard A., additional, Li, He, additional, Ling, Hua, additional, Lipson, Rachel B., additional, Liu, Pengfei, additional, Lovgren, Alysia Kern, additional, López-Giráldez, Francesc, additional, MacMillan, Melissa P., additional, Mangilog, Brian E., additional, Mano, Stacy, additional, Marafi, Dana, additional, Marosy, Beth, additional, Marshall, Jamie L., additional, Martin, Renan, additional, Marvin, Colby T., additional, Mawhinney, Michelle, additional, McGee, Sean, additional, McGoldrick, Daniel J., additional, Mehaffey, Michelle, additional, Mekonnen, Betselote, additional, Meng, Xiaolu, additional, Mitani, Tadahiro, additional, Miyake, Christina Y., additional, Mohr, David, additional, Morris, Shaine, additional, Mullen, Thomas E., additional, Murdock, David R., additional, Murugan, Mullai, additional, Muzny, Donna M., additional, Myers, Ben, additional, Neira, Juanita, additional, Nguyen, Kevin K., additional, Nielsen, Patrick M., additional, Nudelman, Natalie, additional, O’Heir, Emily, additional, O’Leary, Melanie C., additional, Ongaco, Chrissie, additional, Orange, Jordan, additional, Osei-Owusu, Ikeoluwa A., additional, Paine, Ingrid S., additional, Pais, Lynn S., additional, Paschall, Justin, additional, Patterson, Karynne, additional, Pehlivan, Davut, additional, Pelle, Benjamin, additional, Penney, Samantha, additional, Perez de Acha Chavez, Jorge, additional, Pierce-Hoffman, Emma, additional, Poli, Cecilia M., additional, Punetha, Jaya, additional, Radhakrishnan, Aparna, additional, Richardson, Matthew A., additional, Rodrigues, Eliete, additional, Roote, Gwendolin T., additional, Rosenfeld, Jill A., additional, Ryke, Erica L., additional, Sabo, Aniko, additional, Sanchez, Alice, additional, Schrauwen, Isabelle, additional, Scott, Daryl A., additional, Sedlazeck, Fritz, additional, Serrano, Jillian, additional, Shaw, Chad A., additional, Shelford, Tameka, additional, Shively, Kathryn M., additional, Singer-Berk, Moriel, additional, Smith, Joshua D., additional, Snow, Hana, additional, Snyder, Grace, additional, Solomonson, Matthew, additional, Son, Rachel G., additional, Song, Xiaofei, additional, Stankiewicz, Pawel, additional, Stephan, Taylorlyn, additional, Sutton, V. Reid, additional, Sveden, Abigail, additional, Sánchez, Diana Cornejo, additional, Tackett, Monica, additional, Talkowski, Michael, additional, Threlkeld, Machiko S., additional, Tiao, Grace, additional, Udler, Miriam S., additional, Vail, Laura, additional, Valivullah, Zaheer, additional, Valkanas, Elise, additional, VanNoy, Grace E., additional, Wang, Qingbo S., additional, Wang, Gao, additional, Wang, Lu, additional, Wangler, Michael F., additional, Watts, Nicholas A., additional, Weisburd, Ben, additional, Weiss, Jeffrey M., additional, Wheeler, Marsha M., additional, White, Janson J., additional, Williamson, Clara E., additional, Wilson, Michael W., additional, Wiszniewski, Wojciech, additional, Withers, Marjorie A., additional, Witmer, Dane, additional, Witzgall, Lauren, additional, Wohler, Elizabeth, additional, Wojcik, Monica H., additional, Wong, Isaac, additional, Wood, Jordan C., additional, Wu, Nan, additional, Xing, Jinchuan, additional, Yang, Yaping, additional, Yi, Qian, additional, Yuan, Bo, additional, Zeiger, Jordan E., additional, Zhang, Chaofan, additional, Zhang, Peng, additional, Zhang, Yan, additional, Zhang, Xiaohong, additional, Zhang, Yeting, additional, Zhang, Shifa, additional, Zoghbi, Huda, additional, and van den Veyver, Igna, additional

Published
2022
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45. seqr : A web‐based analysis and collaboration tool for rare disease genomics

Author

Pais, Lynn S., primary, Snow, Hana, additional, Weisburd, Ben, additional, Zhang, Shifa, additional, Baxter, Samantha M., additional, DiTroia, Stephanie, additional, O'Heir, Emily, additional, England, Eleina, additional, Chao, Katherine R., additional, Lemire, Gabrielle, additional, Osei‐Owusu, Ikeoluwa, additional, VanNoy, Grace E., additional, Wilson, Michael, additional, Nguyen, Kevin, additional, Arachchi, Harindra, additional, Phu, William, additional, Solomonson, Matthew, additional, Mano, Stacy, additional, O'Leary, Melanie, additional, Lovgren, Alysia, additional, Babb, Lawrence, additional, Austin‐Tse, Christina A., additional, Rehm, Heidi L., additional, MacArthur, Daniel G., additional, and O'Donnell‐Luria, Anne, additional

Published
2022
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46. Variants in Mitochondrial ATP Synthase Cause Variable Neurologic Phenotypes

Author

Zech, Michael, primary, Kopajtich, Robert, additional, Steinbrücker, Katja, additional, Bris, Céline, additional, Gueguen, Naig, additional, Feichtinger, René G., additional, Achleitner, Melanie T., additional, Duzkale, Neslihan, additional, Périvier, Maximilien, additional, Koch, Johannes, additional, Engelhardt, Harald, additional, Freisinger, Peter, additional, Wagner, Matias, additional, Brunet, Theresa, additional, Berutti, Riccardo, additional, Smirnov, Dmitrii, additional, Navaratnarajah, Tharsini, additional, Rodenburg, Richard J.T., additional, Pais, Lynn S, additional, Austin‐Tse, Christina, additional, O'Leary, Melanie, additional, Boesch, Sylvia, additional, Jech, Robert, additional, Bakhtiari, Somayeh, additional, Jin, Sheng Chih, additional, Wilbert, Friederike, additional, Kruer, Michael C, additional, Wortmann, Saskia B., additional, Eckenweiler, Matthias, additional, Mayr, Johannes A., additional, Distelmaier, Felix, additional, Steinfeld, Robert, additional, Winkelmann, Juliane, additional, and Prokisch, Holger, additional

Published
2022
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47. The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

Author

DiStefano, Marina T., primary, Goehringer, Scott, additional, Babb, Lawrence, additional, Alkuraya, Fowzan S., additional, Amberger, Joanna, additional, Amin, Mutaz, additional, Austin-Tse, Christina, additional, Balzotti, Marie, additional, Berg, Jonathan S., additional, Birney, Ewan, additional, Bocchini, Carol, additional, Bruford, Elspeth A., additional, Coffey, Alison J., additional, Collins, Heather, additional, Cunningham, Fiona, additional, Daugherty, Louise C., additional, Einhorn, Yaron, additional, Firth, Helen V., additional, Fitzpatrick, David R., additional, Foulger, Rebecca E., additional, Goldstein, Jennifer, additional, Hamosh, Ada, additional, Hurles, Matthew R., additional, Leigh, Sarah E., additional, Leong, Ivone US., additional, Maddirevula, Sateesh, additional, Martin, Christa L., additional, McDonagh, Ellen M., additional, Olry, Annie, additional, Puzriakova, Arina, additional, Radtke, Kelly, additional, Ramos, Erin M., additional, Rath, Ana, additional, Riggs, Erin Rooney, additional, Roberts, Angharad M., additional, Rodwell, Charlotte, additional, Snow, Catherine, additional, Stark, Zornitza, additional, Tahiliani, Jackie, additional, Tweedie, Susan, additional, Ware, James S., additional, Weller, Phillip, additional, Williams, Eleanor, additional, Wright, Caroline F., additional, Yates, T Michael., additional, and Rehm, Heidi L., additional

Published
2022
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48. Harmonizing variant classification for return of results in the All of Us Research Program

Author

Harrison, Steven M., primary, Austin‐Tse, Christina A., additional, Kim, Serra, additional, Lebo, Matthew, additional, Leon, Annette, additional, Murdock, David, additional, Radhakrishnan, Aparna, additional, Shirts, Brian H., additional, Steeves, Marcie, additional, Venner, Eric, additional, Gibbs, Richard A., additional, Jarvik, Gail P., additional, and Rehm, Heidi L., additional

Published
2021
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50. seqr : a web-based analysis and collaboration tool for rare disease genomics

Author

Pais, Lynn S., primary, Snow, Hana, additional, Weisburd, Ben, additional, Zhang, Shifa, additional, Baxter, Samantha, additional, DiTroia, Stephanie, additional, O’Heir, Emily, additional, England, Eleina, additional, Chao, Katherine, additional, Lemire, Gabrielle, additional, Osei-Owusu, Ikeoluwa, additional, VanNoy, Grace E., additional, Wilson, Michael, additional, Nguyen, Kevin, additional, Arachchi, Harindra, additional, Phu, William, additional, Solomonson, Matthew, additional, Mano, Stacy, additional, O’Leary, Melanie, additional, Lovgren, Alysia, additional, Babb, Lawrence, additional, Austin-Tse, Christina, additional, Rehm, Heidi L., additional, MacArthur, Daniel G., additional, and O’Donnell-Luria, Anne, additional

Published
2021
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