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Review
. 2023 Feb;16(1):e003792.
doi: 10.1161/CIRCGEN.122.003792. Epub 2023 Jan 30.

Proactive Variant Effect Mapping Aids Diagnosis in Pediatric Cardiac Arrest

Brendan J Floyd #  1 , Jochen Weile #  2   3   4 , Prince J Kannankeril  5 , Andrew M Glazer  6 , Chloe M Reuter  7 , Calum A MacRae  8 , Euan A Ashley #  7   9 , Dan M Roden #  10   11   12 , Frederick P Roth #  2   3   4 , Victoria N Parikh #  7
Affiliations
Review

Proactive Variant Effect Mapping Aids Diagnosis in Pediatric Cardiac Arrest

Brendan J Floyd et al. Circ Genom Precis Med. 2023 Feb.
No abstract available

Keywords: calmodulin; cardiovascular disease; clinical decision-making; death, sudden, cardiac; genomics.

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Figures

Figure 1.
Figure 1.
Proactive functional genomics for variant interpretation in CALM1, CALM2, and CALM3. (A) Precision recall curve for variant classifications from Weile et al. displays AUC 0.87 and identifies 71% of pathogenic variants at 90% precision. (B) Variant effect map of CALM1, CALM2, and CALM3 in terms of log10-likelihood ratio, with insets indicating likelihood of pathogenicity for variants evaluated in this report. Columns represent each amino acid position with each row representing a different variant at that position. (C) EKG demonstrating long QT (525 ms) in Case 1. (D) Ventricular ectopy consistent with catecholaminergic polymorphic tachycardia at peak exercise in Case 1. (E) Pedigree demonstrating complex family history of cardiomyopathy and sudden death despite de novo status of the CALM1 VUS in Case 3.
See this image and copyright information in PMC

References

    1. van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I. Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. Neth Heart J. 2019; 27:304–309. - PMC - PubMed
    1. Weile J, Sun S, Cote AG, Knapp J, Verby M, Mellor JC, Wu Y, Pons C, Wong C, van Lieshout N, et al. A framework for exhaustively mapping functional missense variants. Mol Syst Biol. 2017; 13:957. - PMC - PubMed
    1. Wu Y, Weile J, Cote AG, Sun S, Knapp J, Verby M, Roth FP. A web application and service for imputing and visualizing missense variant effect maps. Bioinformatics. 2019; 35:3191–3193. - PMC - PubMed
    1. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17:405–423. - PMC - PubMed
    1. Tavtigian SV, Greenblatt MS, Harrison SM, Nussbaum RL, Prabhu SA, Boucher KM, Biesecker LG, ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI). Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework. Genet Med. 2018; 20:1054–1060. - PMC - PubMed

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