Dataset Information

Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions.

ABSTRACT:

Background

As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings.

Methods

We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering.

Results

For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches.

Conclusions

Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing.

SUBMITTER: Josephs KS

PROVIDER: S-EPMC10594882 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions.

Josephs Katherine S KS Roberts Angharad M AM Theotokis Pantazis P Walsh Roddy R Ostrowski Philip J PJ Edwards Matthew M Fleming Andrew A Thaxton Courtney C Roberts Jason D JD Care Melanie M Zareba Wojciech W Adler Arnon A Sturm Amy C AC Tadros Rafik R Novelli Valeria V Owens Emma E Bronicki Lucas L Jarinova Olga O Callewaert Bert B Peters Stacey S Lumbers Tom T Jordan Elizabeth E Asatryan Babken B Krishnan Neesha N Hershberger Ray E RE Chahal C Anwar A CAA Landstrom Andrew P AP James Cynthia C McNally Elizabeth M EM Judge Daniel P DP van Tintelen Peter P Wilde Arthur A Gollob Michael M Ingles Jodie J Ware James S JS

Genome medicine 20231023 1

<h4>Background</h4>As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings.<h4>Methods</h4>We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pai ...[more]

PMID: 37872640

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Project description:BackgroundKnowledge translation platforms (KTPs), which are partnerships between policymakers, stakeholders, and researchers, are being established in low- and middle-income countries (LMICs) to enhance evidence-informed health policymaking (EIHP). This study aims to gain a better understanding of the i) activities conducted by KTPs, ii) the way in which KTP leaders, policymakers, and stakeholders perceive these activities and their outputs, iii) facilitators that support KTP work and challenges, and the lessons learned for overcoming such challenges, and iv) factors that can help to ensure the sustainability of KTPs.MethodsThis paper triangulated qualitative data from: i) 17 semi-structured interviews with 47 key informants including KTP leaders, policymakers, and stakeholders from 10 KTPs; ii) document reviews, and iii) observation of deliberations at the International Forum on EIHP in LMICs held in Addis Ababa in August 2012. Purposive sampling was used and data were analyzed using thematic analysis.ResultsDeliberative dialogues informed by evidence briefs were identified as the most commendable tools by interviewees for enhancing EIHP. KTPs reported that they have contributed to increased awareness of the importance of EIHP and strengthened relationships among policymakers, stakeholders, and researchers. Support from policymakers and international funders facilitated KTP activities, while the lack of skilled human resources to conduct EIHP activities impeded KTPs. Ensuring the sustainability of EIHP initiatives after the end of funding was a major challenge for KTPs. KTPs reported that institutionalization within the government has helped to retain human resources and secure funding, whereas KTPs hosted by universities highlighted the advantage of autonomy from political interests.ConclusionsThe establishment of KTPs is a promising development in supporting EIHP. Real-time lesson drawing from the experiences of KTPs can support improvements in the functioning of KTPs in the short term, while making the case for sustaining their work in the long term. Lessons learned can help to promote similar EIHP initiatives in other countries.

Dataset Information

Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions.

Background

Methods

Results

Conclusions

Publications

Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions.

Similar Datasets

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