Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.
Genetics in Medicine. Published online May 11, 2017. doi:10.1038/gim.2017.37Consistency of BRCA1 and BRCA2 variant classifications among clinical diagnostic laboratories.
Lincoln SE, Yang S, Cline MS, Kobayashi Y, Zhang C, Topper S, Haussler D, Paten B, Nussbaum RL.
JCO Precision Oncology. Published online April 11, 2017. doi:10.1200/PO.16.00020 Pathogenic variant burden in the ExAC database: An empirical approach to evaluating population data for clinical variant interpretation.
Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.
Genome Medicine. 2017, 9, 13. doi:10.1186/S13073-017-0403-7 Clinical genetics testing laboratories have a remarkably low rate of clinically significant discordance when interpreting variants in hereditary cancer syndrome genes.
Nussbaum RL, Yang S, Lincoln SE.
Journal of Clinical Oncology. Published online January 30, 2017. doi:10.1200/JCO.2016.70.9451 Data sharing and reproducible clinical genetic data: Success and challenges.
Yang S, Cline M, Zhang C, Paten B, Lincoln SE.
Pacific Symposium on Biocomput. 2016, 22, 166-176. doi:10.1142/9789813207813_0017 Clinical genetic testing for the cardiomyopathies and arrhythmias: A systematic framework for establishing clinical validity and addressing genotypic and phenotypic heterogeneity.
Garcia J, Tahiliani J, Johnson NM, Aguilar S, Beltran D, Daly A, Decker E, Haverfield E, Herrera B, Murillo L, Nykamp K, Topper S.
Frontiers in Cardiovascular Medicine. 2016, 3(20). doi:10.3389/fcvm.2016.00020 Germline hemizygous deletion of CDKN2A–CDKN2B locus in a patient presenting with Li–Fraumeni syndrome.
Chan SH, Lim WK, Michalski ST, Lim JQ, Binte Ishak ND, Met-Domestici M, Chuan Young CN, Vikstrom K, Esplin ED, Fulbright J, Ang MK, Wee J, Sittampalam K, Farid M, Lincoln SE, Itahana K, Abdullah S, Teh BT, Ngeow J.
NPJ Genomic Medicine. 2016, 1, 16015. doi:10.1038/npjgenmed.2016.15 Who pays? Coverage challenges for cardiovascular genetic testing in U.S. patients.
Spoonamore K, Johnson NM.
Frontiers in Cardiovascular Medicine. 2016, 3(14). doi:10.3389/fcvm.2016.00014 Comprehensive versus targeted genetic testing in children with hypertrophic cardiomyopathy.
Bales ND, Johnson NM, Judge DP, Murphy AM.
Pediatric Cardiology. 2016, 37(5), 845. doi:10.1007/s00246-016-1358-y An individual with both MUTYH-associated polyposis and Lynch syndrome identified by multi-gene hereditary cancer panel testing: A case report.
Cohen SA, Tan CA, Bisson R.
Frontiers in Genetics. 2016, 7, 1. doi:10.3389/fgene.2016.00036 Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.
Tan CA, Rabideau M, Blevins A, Westbrook MJ, Ekstein T, Nykamp K, Deucher A, Harper A, Demmer L.
American Journal of Medical Genetics Part A. 2016, 170(6), 1552-4833. doi:10.1002/ajmg.a.37611 Genetic counselors in startup companies: Redefining the genetic counselor role.
Rabideau MM, Wong K, Gordon ES, Ryan L.
Journal of Genetic Counselling. 2016, 25(4), 649–657. doi:10.1007/s10897-015-9923-8 Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment.
Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, Horick N, Yang S, Shannon KM, Tung N, Ford JM, Lincoln SE, Ellisen LW.
JAMA Oncology. 2015, 1(7), 943-951. doi:10.1001/jamaoncol.2015.2690 A systematic comparison of traditional and multigene panel testing for hereditary breast and ovarian cancer genes in more than 1000 patients.
Lincoln S, Kobayashi Y, Anderson M, Yang S, Desmond AJ, Mills MA, Nilsen GB, Jacobs KB, Monzon FA, Kurian AW, Ford JM, Ellisen LW.
The Journal of Molecular Diagnostics. 2015, 17(5), 533-544. doi:10.1016/j.jmoldx.2015.04.009 Low-level constitutional mosaicism of a de novoBRCA1 gene mutation.
Friedman E, Efrat N, Soussan-Gutman L, Dvir A, Kaplan Y, Ekstein T, Nykamp K, Powers M, Rabideau M, Sorenson J, Topper S.
British Journal of Cancer. 2015, 112, 765–768. doi:10.1038/bjc.2015.14 A Python package for parsing, validating, mapping and formatting sequence variants using HGVS nomenclature.
Hart RK, Rico R, Hare E, Garcia J, Westbrook J, Fusaro VA.
Bioinformatics. 2015, 31(2), 268-270. doi:10.1093/bioinformatics/btu630 Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment.
Kurian AW, Hare EE, Mills MA, Kingham KE, McPherson L, Whittemore AS, McGuire V, Ladabaum U, Kobayashi Y, Lincoln SE, Cargill M, Ford JM.
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PRESENTATIONSCopy number variant analysis enhances molecular diagnostic yield of inborn errors of metabolism Metabolic pathognomonics: Incorporating disease-specific biochemical data improves variant interpretation for inherited metabolic disorders
POSTERSDetermining the clinical value of germline genetic testing coupled with tumor mutation profiling Need for re-evaluation of current guidelines based on results from germline genetic testing in prostate cancer Unexpected germline mutations in a pan-cancer analysis including sarcoma, renal, and other cancers
PRESENTATIONPathogenic variants in calmodulin associated with resuscitated childhood cardiac arrest
POSTERSExpanded gene panel utilization in women with breast cancer: identification and intervention beyond breast cancer risk Hereditary cancer risk: A growing body of evidence supporting broader testing Breast surgeon consultation with remote genetic counselor improves clinical decision-making
POSTERSAttitudes of healthy early adopters toward professional genome sequencing: Observations from the PeopleSeq Consortium The benefit of a medically actionable genetic screening panel in healthy individuals: A case report Canavan disease research: Forming a Patient Insights Network for the Canavan disease community CNV analysis of ACADM enhances yield in the molecular diagnosis of medium-chain acyl-CoA dehydrogenase deficiency Contiguous 2p16.3p21 gene deletion including EPCAM, MSH2, and MSH6 identified with next-generation sequencing Co-occurrence of pathogenic variants in MPZ and LRSAM1 in Charcot-Marie-Tooth disease: Implications for genetic counseling for multi-gene panel testing Detection of a novel complex rearrangement in KCNH2 with next-generation sequencing in a clinical laboratory Genetic information for healthy individuals: Developing a medically actionable genetic screening panel Glycine missense variants in the COL3A1 triple-helix domain: Assessing functional domain data during clinical variant interpretation Harmonizing variant interpretation for sequence and copy number changes within individual genes in clinical diagnostic testing Leveraging phenotype ontologies to improve variant interpretation by factoring in phenotype specificity Metabolic pathognomonics: incorporating disease-specific biochemical data improves variant interpretation for inherited metabolic disorders Molecular diagnosis of primary ciliary dyskinesia: Experience from a clinical laboratory One of these things is not like the other: Clinically actionable discordance between germline sequencing and somatic tumor profiling in cancer patients PMS2 pseudogene and disambiguation: Technically challenging, clinically critical Potential of predispositional genetic screening for dominant actionable disorders: prevalence of genomic variants in 16,000 individuals
PRESENTATIONSThe spectrum of pathogenic variants underlying multiple conditions in 80,000 patients: Implications for test implementation, utilization and validation Tracing the dark matter: Prevalence of copy number and structural variants across Mendelian disorders
POSTERSAccurate detection of copy-number changes in the highly conserved regions of PMS2 using NGS Attitudes regarding personal genomic sequencing among healthy early adopters: Findings from the PeopleSeq Consortium Creating a medically actionable genetic screening panel for healthy individuals Evaluating the strength of evidence for gene-condition relationships: impact on multi-gene panel testing design Germline hemizygous deletion of CDKN2A-CDKN2B locus in a patient presenting with Li-Fraumeni syndrome (also published in npj Genomics Medicine) Glycine missense variants in the COL3A1 triple helix domain: assessing functional domain data during clinical variant interpretation Mammalian species conservation data and the implication for clinical variant classification Molecular follow-up of a newborn screening positive case of medium-chain acyl–coenzyme A dehydrogenase deficiency identified two ACADM variants:
POSTERSMammalian species conservation data and the implications for clinical variant classification Novel large rearrangement of RAD51D in an ovarian and breast cancer family Inherited cardiomyopathies in the pediatric population: what molecular testing reveals
presentationsBioinformatics for genetic counselors, version 2.0 Creating a medically actionable genetic screening panel for healthy individuals A novel approach to lab-based clinical genetic counseling Hereditary genetic testing: current and future challenges
posterCopy number variation in clinical tests for inherited cardiomyopathies and arrhythmias
presentationWhat have public databases taught us about variant classification?
postersVariant classifications for BRCA1 and BRCA2 are substantially concordant across major clinical testing laboratories The expanding phenotype of PALB2-related cancer: clinical presentations of 144 identified carriers
presentationMosaic genetic variants in hereditary germline genetic testing: the expected and the unexpected
posterClinical presentation and management considerations for 77 breast cancer patients with germline PALB2 mutations
posterClinical actionability of panel tests for genes in the NCCN Guidelines for Hereditary Breast and Ovarian Cancer Clinical presentations of 111 patients with germline PALB2 mutations: Looking beyond breast and ovarian cancer
posterPreparing for the unexpected: Panel-based testing of ovarian cancer patients reveals actionable variants in non-canonical genes
postersClinical actionability of non-BRCA1/2 mutations uncovered in multigene tests for hereditary breast cancer Variant classifications for BRCA1 and BRCA2 are highly concordant across major clinical testing laboratories Clinical presentation and management considerations for 68 breast cancer patients with germline PALB2 mutations
postersAllele frequency distribution of pathogenic sequence variants in ExAC and the implications for clinical genetic testing Expanding phenotypes of cancer predisposition genes: CDKN2A Detection of novel Alu insertions by next-generation sequencing of hereditary cancer genes Challenges of content expansion with panel testing: incorporating informatics into the clinical report Rare disease diagnosis obstacles: patient perspectives and physician findings To include or not to include: RASopathy genes in cardiomyopathy genetic testing To confirm or not to confirm, that is the question: a rigorous approach to evaluating the importance of Sanger confirmation of clinical NGS findings
presentationDon't believe everything you hear: Variant classifications for BRCA1 and BRCA2 are highly concordant across major clinical testing laboratories
postersAn opportunity or dilemma? Customizable panel tests and clinician ordering behavior Establishing and evaluating a framework for describing variant evidence in clinical genomic reports Sherloc- Evaluation of a score-based implementation of the AMP-ACMG ISV guidelines in a scalable genetic diagnostic laboratory
PresentationsAnalytic validation standards for NGS assays and new reference materials needed A rigorous approach to evaluating the importance of Sanger Confirmation of NGS findings
postersClinical actionability of multigene tests for hereditary breast and ovarian cancer Integration of the ACMG ISV guidelines into clinical variant analysis and interpretation processes- A model for diagnostic standardization Moving beyond the 1%- incorporating the Exome Aggregation Consortium (ExAC) data into variant interpretation and classification To confirm or not confirm, that is the question: A rigorous approach to evaluating the importance of sanger confirmation of clinical NGS findings Understanding psychiatrists’ perceptions surrounding psychiatric genetics and genetic counseling services
PresentationsFinding just right- Balancing payer and provider goals for hereditary genetic testing Next generation sequencing- Challenges and strategies in testing patients with circulating hematopoietic malignancies Validation of clinical genetic tests - or – How to stop worrying and love the data!