Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions
Zhang X, Walsh R, Whiffin N, Buchan R, Midwinter W, Wilk A, Govind R, Li N, Ahmad M, Mazzarotto F, Roberts A, Theotokis PI, Mazaika E, Allouba M, de Marvao A, Pua CJ, Day SM, Ashley E, Colan SD, Michels M, Pereira AC, Jacoby D, Ho CY, Olivotto I, Gunnarsson GT, Jefferies JL, Semsarian C, Ingles J, O’Regan D, Aguib Y, Yacoub MH, Cook SA, Barton PJR, Bottolo L, Ware JS. Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions. Genetics In Medicine 2020, 23: 69-79. PMID: 33046849, PMCID: PMC7790749, DOI: 10.1038/s41436-020-00972-3.Peer-Reviewed Original ResearchConceptsRare missense variantsCardiac conditionsSevere adverse outcomesMissense variantsDisease-specific informationAdverse outcomesClinical severityPatient outcomesHypertrophic cardiomyopathyAge 60Disease statusDisease specificityFunction variantsBenign variantsCardiomyopathyRare variationProportion of variantsDisease-associated variantsOutcomesVariant interpretationProbability of pathogenicityGene-disease relationshipsVariant pathogenicity predictionPatientsArrhythmiasHypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry
Marstrand P, Han L, Day SM, Olivotto I, Ashley EA, Michels M, Pereira AC, Wittekind SG, Helms A, Saberi S, Jacoby D, Ware JS, Colan SD, Semsarian C, Ingles J, Lakdawala NK, Ho CY. Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry. Circulation 2020, 141: 1371-1383. PMID: 32228044, PMCID: PMC7182243, DOI: 10.1161/circulationaha.119.044366.Peer-Reviewed Original ResearchConceptsLeft ventricular systolic dysfunctionVentricular ejection fractionComposite outcomeHypertrophic cardiomyopathyNatural historyEjection fractionLeft ventricular cavity sizeVentricular systolic dysfunctionPredictor of prognosisVentricular cavity sizeProportional hazards modelSignificant predictorsSystolic dysfunctionMedian timeAtrial fibrillationSpecialty centersSarcomeric variantsHazards modelIncident developmentPatientsEnd stageRelative rarityPrognosisOutcomesPredictors