Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings

Reble, Emma; Salazar, Mariana Gutierrez; Zakoor, Kathleen-Rose; Khalouei, Sam; Clausen, Marc; Kodida, Rita; Shickh, Salma; Mighton, Chloe; Cohn, Iris; Schrader, Kasmintan A.; Kim, Raymond H.; Lerner‐Ellis, Jordan; Bombard, Yvonne

doi:10.1007/s00439-020-02220-9

Cited by 13 publications

(10 citation statements)

References 28 publications

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“…Exome sequencing, data processing and variant ltration, and curated gene and variant lists for SF categories analyzed was performed as previously reported (Reble et al 2021). Filtered variants were classi ed in accordance with the "Standards and Guidelines for the Interpretation of Sequence Variants" developed by the ACMG and AMP (Richards et al 2015).…”

Section: Interpreting Exome Sequencing Resultsmentioning

confidence: 99%

“…On average, exome sequencing of all clinically relevant genes can result in over 62,000 variants identi ed per patient (Reble et al 2021). Even with stringent variant ltering parameters, the sheer volume of variants returned for primary indications and SFs presents a reporting challenge for diagnostic laboratories.…”

Section: Introductionmentioning

confidence: 99%

“…Even with stringent variant ltering parameters, the sheer volume of variants returned for primary indications and SFs presents a reporting challenge for diagnostic laboratories. This is further complicated by the majority of variants that are classi ed as variants of uncertain signi cance (Reble et al 2021; Federici and Soddu 2020). In addition, not all SFs fall into the recommended ACMG-AMP classi cation categories (pathogenic, likely pathogenic, uncertain signi cance, likely benign, and benign) (Richards et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings

Sam

Reble²,

Kodida³

et al. 2022

Hum Genet

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Genomic sequencing (GS) can reveal secondary ndings (SFs), ndings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically signi cant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically signi cant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in 3 phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative re nement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary and secondary ndings, with in-depth details of each nding. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically signi cant SFs to patients and providers, facilitating clinical management of GS results.

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Section: Interpreting Exome Sequencing Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings

Sam

Reble²,

Kodida³

et al. 2022

Hum Genet

Self Cite

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“…A first step would be to develop a consensus list of secondary findings of pharmacogenes to avoid disparities in what information is offered or reported between laboratories (Bombard et al, 2020;Reble et al, 2021). Then, clinical PGx testing labs that include genes in their test panels with secondary findings could offer patients the option of receiving a separate report on secondary findings (Brothers et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Revisiting Secondary Information Related to Pharmacogenetic Testing

Haga

2021

Front. Genet.

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Incidental or secondary findings have been a major part of the discussion of genomic medicine research and clinical applications. For pharmacogenetic (PGx) testing, secondary findings arise due to the pleiotropic effects of pharmacogenes, often related to their endogenous functions. Unlike the guidelines that have been developed for whole exome or genome sequencing applications for management of secondary findings (though slightly different from PGx testing in that these refer to detection of variants in multiple genes, some with clinical significance and actionability), no corresponding guidelines have been developed for PGx clinical laboratories. Nonetheless, patient and provider education will remain key components of any PGx testing program to minimize adverse responses related to secondary findings.

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“…This is clearly a limited subset of “actionable” disorders that include a large number with anticipatory management guidelines and treatments unrelated to pathogenesis. (Milko et al, 2019; Cehyan‐Birsoy et al, 2019; Reble et al, 2020; Adhikari et al, 2020; Richer & Laberge, 2019; Clinical Actionability Curations, https://www.clinicalgenome.org/curation-activities/clinical-actionability/browse-curations/, https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html). As the published literature demonstrates, however, there is no general agreement on what constitutes an “actionable” disorder.…”

Section: Discussionmentioning

confidence: 99%

An online compendium of treatable genetic disorders

Bick

Dimmock

et al. 2020

American J of Med Genetics Pt C

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More than 4,000 genes have been associated with recognizable Mendelian/monogenic diseases. When faced with a new diagnosis of a rare genetic disorder, health care providers increasingly turn to internet resources for information to understand the disease and direct care. Unfortunately, it can be challenging to find information concerning treatment for rare diseases as key details are scattered across a number of authoritative websites and numerous journal articles. The website and associated mobile device application described in this article begin to address this challenge by providing a convenient, readily available starting point to find treatment information. The site, http://rx-genes.com (https://www.rx-genes.com/), is focused on those conditions where the treatment is directed against the mechanism of the disease and thereby alters the natural history of the disease. The website currently contains 633 disease entries that include references to disease information and treatment guidance, a brief summary of treatments, the inheritance pattern, a disease frequency (if known), nonmolecular confirmatory testing (if available), and a link to experimental treatments. Existing entries are continuously updated, and new entries are added as novel treatments appear in the literature.

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Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings

Cited by 13 publications

References 28 publications

A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings

A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings

Revisiting Secondary Information Related to Pharmacogenetic Testing

An online compendium of treatable genetic disorders

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