2025
Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models
Halder S, Bellitto J, Rynkiewicz M, Cheung F, Liu D, Firlar I, Bongiorno A, Barry M, Sewanan L, Moore J, Lehman W, Campbell S. Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models. The Journal Of Precision Medicine Health And Disease 2025, 2: 100008. DOI: 10.1016/j.premed.2025.100008.Peer-Reviewed Original ResearchIn vitro motilityFilament motilityContext of cardiomyopathyVariant classificationGenetic screeningTwitch contraction forceComputational pipelineMyosin activityEvaluate pathogenicityDiversity changesFunctional studiesIn silicoTropomyosinTPM1VUSMotilityInherited cardiomyopathyCa2+ sensitivityVariantsIn vitro modelIn vitro dataReduced abilityIPSC-derived cardiomyocytesLow Ca2+Ca2+Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity
Novotny S, Yoo N, Chen J, Granoth M, Kohli-Pamnani A, Hsu F, Rodenas M, Steele R, Kaman K, Soffer G, Price C, Kuster J, Kang I, Osmani L, Shin J. Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity. Clinical Immunology 2025, 277: 110513. PMID: 40354868, DOI: 10.1016/j.clim.2025.110513.Peer-Reviewed Original ResearchInborn errors of immunityErrors of immunityGenetic variantsInborn errorsAssociation of clinical manifestationsGene clusterGene functionStudy evaluated associationsImmune alterationsDiagnostic challengeClinical manifestationsImmunological profileGenetic testingVUSGenesImmunological characteristicsImmune functionLaboratory dataImmunityVariantsAssociationPatientsModeling thoracic aortic genetic variants in the zebrafish: useful for predicting clinical pathogenicity?
Prendergast A, Sheppard M, Famulski J, Nicoli S, Mukherjee S, Sips P, Elefteriades J. Modeling thoracic aortic genetic variants in the zebrafish: useful for predicting clinical pathogenicity? Frontiers In Cardiovascular Medicine 2025, 12: 1480407. PMID: 40066353, PMCID: PMC11892108, DOI: 10.3389/fcvm.2025.1480407.Peer-Reviewed Original ResearchPathogenicity of VUSProportion of variantsMedical genetic testingCausal genesPathogenicity assessmentClinical pathogensTested pathogensGenetic variantsCausative genesTAAD casesGenesGenetic defectsGenetic testingThoracic aortic aneurysmHeritable genetic defectsImpact cardiovascular morbidityPathogensVUSAortic aneurysmCardiovascular morbidityVariantsZebrafishTAADClinical applicationEnhance patient care
2024
Clinical Effectiveness of Genetic Testing Guidelines in Patients with Thoracic Aortic Aneurysms
Erez E, Acuna Higaki A, Cupo M, Phu T, Verma S, Assi R, Vallabhajosyula P. Clinical Effectiveness of Genetic Testing Guidelines in Patients with Thoracic Aortic Aneurysms. Journal Of Thoracic And Cardiovascular Surgery 2024 PMID: 39321868, DOI: 10.1016/j.jtcvs.2024.09.026.Peer-Reviewed Original ResearchFeatures of connective tissue diseaseThoracic aortic diseaseConnective tissue diseaseThoracic aortic aneurysmGenetic testing guidelinesSyndromic featuresMutation rateFamily historyVUS rateAortic aneurysmPrimary genesGenetic testingAssociated with thoracic aortic diseaseThoracic aorta diameterTesting guidelinesAorta diameterPathogen mutation rateAortic diseaseRisk stratificationSecondary genesPathogenic mutationsTissue diseaseClinical effectsVUSGenesClassifying pathogenicity of TPM1 variants of unknown significance using in vitro and in silico approaches
Campbell S, Creso J, Firlar I, Halder S, Lehman W, Rynkiewicz M, Moore J. Classifying pathogenicity of TPM1 variants of unknown significance using in vitro and in silico approaches. Journal Of Cardiac Failure 2024, 30: s3. DOI: 10.1016/j.cardfail.2023.11.005.Peer-Reviewed Original ResearchHypertrophic cardiomyopathyUnknown significanceContractile forceOngoing clinical challengeFirst-degree relativesGenetic testing yieldSlowing of relaxationViral exposureContractile weaknessClinical challengeHypercontractile phenotypeHCM mutationsMyofilament activityHeart tissueMild phenotypeFurther studiesContractile behaviorSignificant increaseHEHTTesting yieldDCM mutationsMinimal effectVUSPathogenicityPhenotype
2021
Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation
Thompson AD, Helms AS, Kannan A, Yob J, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Mazzarotto F, Olivotto I, Ho CY, Day SM. Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation. Genetics In Medicine 2021, 23: 1281-1287. PMID: 33782553, PMCID: PMC8257482, DOI: 10.1038/s41436-021-01134-9.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyClinical riskMissense variantsSarcomeric Human Cardiomyopathy RegistryHigh clinical riskClinical risk stratificationAdverse eventsComposite endpointRisk stratificationHCM patientsCommon causePatientsLoss of functionUncertain significanceMYBPC3Missense VUSCardiomyopathyHigh rateSubstantial numberSupportive evidenceVUSRiskVariant interpretationEvent analysisMethodsAmong
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply