Evidence map›Paper›PMID 30293987›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019

Identification of clinically actionable variants from genome sequencing of families with congenital heart disease.

Dimuthu Alankarage, Eddie Ip, Justin O Szot, Jacob Munro, Gillian M Blue, Katrina Harrison, Hartmut Cuny, Annabelle Enriquez, Michael Troup, David T Humphreys and 11 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

21 authors.

Dimuthu AlankarageVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Eddie Ip *Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Justin O Szot *Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Jacob MunroVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Gillian M BlueVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Katrina HarrisonGenetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Hartmut CunyVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Annabelle EnriquezVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Michael TroupVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
David T HumphreysVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Meredith WilsonDivisions of Genetic Medicine and Child and Adolescent Health, University of Sydney, Sydney, Australia.
Richard P HarveyVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Gary F ShollerHeart Centre for Children, The Children's Hospital at Westmead, Sydney, Australia.
Robert M GrahamVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Joshua W K HoVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Edwin P KirkSydney Children's Hospital, Sydney, Australia.
Nicholas PachterGenetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Gavin ChapmanVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
David S Winlaw *Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Eleni Giannoulatou *Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Sally L Dunwoodie *Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia. s.dunwoodie@victorchang.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCongenital heart disease (CHD) affects up to 1% of live births. However, a genetic diagnosis is not made in most cases. The purpose of this study was to assess the outcomes of genome sequencing (GS) of a heterogeneous cohort of CHD patients.

methodsNinety-seven families with probands born with CHD requiring surgical correction were recruited for genome sequencing. At minimum, a proband-parents trio was sequenced per family. GS data were analyzed via a two-tiered method: application of a high-confidence gene screen (hcCHD), and comprehensive analysis. Identified variants were assessed for pathogenicity using the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines.

resultsClinically relevant genetic variants in known and emerging CHD genes were identified. The hcCHD screen identified a clinically actionable variant in 22% of families. Subsequent comprehensive analysis identified a clinically actionable variant in an additional 9% of families in genes with recent disease associations. Overall, this two-tiered approach provided a clinically relevant variant for 31% of families.

conclusionsInterrogating GS data using our two-tiered method allowed identification of variants with high clinical utility in a third of our heterogeneous cohort. However, association of emerging genes with CHD etiology, and development of novel technologies for variant assessment and interpretation, will increase diagnostic yield during future reassessment of our GS data.

Indexed as

Base SequenceChromosome MappingCohort StudiesExomeFamilyFemaleGenetic Predisposition to DiseaseGenetic TestingGenetic VariationGenomicsHeart Defects, CongenitalHigh-Throughput Nucleotide SequencingHumansMaleMutationParentsACMGclinical utilitycongenital heart diseasegenetic diagnosisgenome sequencing

Identifiers

PMID30293987

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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.