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 predictionPatientsArrhythmiasSpatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy
Helms AS, Thompson AD, Glazier AA, Hafeez N, Kabani S, Rodriguez J, Yob JM, Woolcock H, Mazzarotto F, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Olivotto I, Ho CY, Day SM. Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy. Circulation Genomic And Precision Medicine 2020, 13: 396-405. PMID: 32841044, PMCID: PMC7676622, DOI: 10.1161/circgen.120.002929.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyPathogenic variantsClinical outcomesSarcomeric Human Cardiomyopathy RegistryTruncating variantsHypertrophic cardiomyopathy cohortAdverse event ratesSimilar clinical severityDetailed genotype-phenotype correlationRat ventricular myocytesC10 domainCardiomyopathy cohortGenotype-phenotype correlationMyofilament incorporationFamilial hypertrophic cardiomyopathyClinical severityGenotyped patientsCommon causeMorphological severityTime-event analysisCardiac morphologyPatientsLoss of functionCardiomyopathyVentricular myocytes