Evidence map›Paper›PMID 36578016›Full record

ArticleGenome medicine2022

The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic.

Fergus Stafford, Neesha Krishnan, Ebony Richardson, Alexandra Butters, Sophie Hespe, Charlotte Burns, Belinda Gray, Caroline Medi, Natalie Nowak, Julia C Isbister and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

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

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

2 · The registry

The trial behind it

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

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

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. What Should a Clinical Cardiologist Know About Cardiogenetics?Journal of the American Heart Association · 2025
    Review
  10. Dilated cardiomyopathy in patients with PRDM16 haploinsufficiency.Journal of molecular medicine (Berlin, Germany) · 2025
    Article
  11. Review
  12. Article
  13. Review
  14. Public's perception and attitude toward genetic testing in Jazan region.Journal of family medicine and primary care · 2024
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Cardiogenetics: Closing the knowledge gap in India.Indian pacing and electrophysiology journal
    Article
4 · The record

Corrections and comments

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

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Fergus Stafford *Cardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
Neesha Krishnan *Cardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
Ebony RichardsonCardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
Alexandra ButtersCardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
Sophie HespeCentre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Charlotte BurnsFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Belinda GrayFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Caroline MediDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Natalie NowakFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Julia C IsbisterFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Hariharan RajuDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
David RichmondFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Mark P RyanDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Emma S SingerFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Raymond W SyFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Laura YeatesCardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
Richard D BagnallFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Christopher SemsarianFaculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Jodie InglesCardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia. jodie.ingles@populationgenomics.org.au.ORCID 0000-0002-4846-7676
The University of Sydney · AURoyal Prince Alfred Hospital · AUGarvan Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and is primarily indicated for screening of at-risk relatives. Here, we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialised clinic and identify those with the highest likelihood of having a monogenic disease.

methodsA retrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020 was performed. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset, and severe phenotype, whereas low-scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated.

resultsA total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15 to 20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing.

conclusionsResearch-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease.

Indexed as

Genetic TestingHeart DiseasesHumansPhenotypeRetrospective StudiesGenetic testingInherited cardiac conditionsSudden cardiac death

Identifiers

PMID36578016
PMCPMC9795753
OpenAlexW4313417185

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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