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Cardiogenetics Testing Reference Guide December 2018

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Cardiogenetics Testing reference guide December 2018 Why Choose Ambry More than 1 in 200 people have an inherited cardiovascular condition. Ambry’s mission is to provide the most advanced genetic testing information available to help you identity those at-risk and determine the best treatment options. If we know a patient has a disease-causing genetic change, not only does it mean better disease management, it also indicates that we can test others in the family and provide them with potentially life-saving information. Diseases and Testing Options cardiomyopathies arrhythmias Hypertrophic Cardiomyopathy (HCMNext) Catecholaminergic Polymorphic Ventricular Dilated Cardiomyopathy (DCMNext) Tachycardia (CPVTNext) Arrhythmogenic Right Ventricular Long QT Syndrome, Short QT Syndrome, Cardiomyopathy (ARVCNext) Brugada Syndrome (LongQTNext, RhythmNext) Cardiomyopathies (CMNext, CardioNext) Arrhythmias (RhythmNext, CardioNext) other cardio conditions Transthyretin Amyloidosis (TTR) familial hypercholesterolemia Noonan Syndrome (NoonanNext) and lipid disorders Hereditary Hemorrhagic Telangiectasia Familial Hypercholesterolemia (FHNext) (HHTNext) Sitosterolemia (Sitosterolemia Panel) Comprehensive Lipid Menu thoracic aortic aneurysms (CustomNext-Cardio) and dissections Familial Chylomicronemia Syndrome (FCSNext) Thoracic Aneurysms and Dissections, aortopathies (TAADNext) Marfan Syndrome (TAADNext) Ehlers-Danlos Syndrome (TAADNext) Targeted Panels Gene Comparison ALL PANELS HAVE A TURNAROUND TIME OF 2-3 WEEKS arrhythmias CPVTNext CPVTNext CASQ2, RYR2 CASQ2, CALM1 RYR2 TRDN CALM1 RhythmNext TRDN CACNA2D1, CACNB2, LongQTNext RhythmNext DES, DSC2, DSG2, DSP, ANK2, AKAP9, CACNA1C, CACNA2 GPD1L, HCDN1,4 C, AJUCPN,B 2, CALM2, CALM3, CAV3, LongQTNext DES, DSC KCND3, K2C, DNSEG3,2 K, CDNSPJ8, , AKNCKN2E, 1A, KACPN9E,2 C, AKCNHA21C, , GPD1L, H LMNA, NCKNX42, .J5U, PP,L N, CKACLNMJ52, ,K CCANLJM2,3 K, CANVQ31,, KCND3, PKP2, SKCN1E03A, K, SCCNNJ81B, , KSCNE41B, ,K SCCNNE52A, ,K SCNNTHA21, LMSNCAN, 3NBK, XTE2C.5R, LP,L TNB, X5, KCNJ5, KCNJ2, KCNQ1, PKPT2M, SECMN4103A, T, RSPCMN14B, SCN4B, SCN5A, SNTA1 SCN3B, TECRL, TBX5, TMEM43, TRPM4 cardiomyopathies ARVCNext ARVCNex CMNext includes all genes seen here DS t G2, DSC2, and CRYAB, EMD, HCM4 JUP, P KP2, CMNext includes all genes seen here DS TMEGM24, 3D,S RCY2R, 2 and CRYAB, EMD, HCM4 JUP, PKP2, TMEM43, RYR2 DES, DSP, LMNA, SCN5A DES, DSP, PLN LMNA, SCN5A PL DCMNext N ABCC9, ALMS1, HCMNext ACTC1, ACTN2, ALPK3, FHL1, GLA, BAG3, DMD, DOLK DCMNext , ANKRD1, CSRP3, JPH2, MYL2, MYL3, FAKBRCPC, 9L,A AMLMA4S,1 ,L D HCMNext B3, AFLCNTC,1 ,L ACMTPN22, , APLRPKA3,G F2H, LP1T, PGNLA11,, BNAKGX32, .D5M, RDB,M D2O0L,K, MANYKBRPDC31,, CMSYRHP36,, JPH2, MYRILT21,, MSOYSL13, FKTRAPZ, ,L AMA4, LD TBX20, TTNB3 , MYHFL7N, CM, YLAPNM, PN2E, XN, PRKAG2, PTPN11, NKX2.5, RBM20, RAMFY1,B TPCCA3,P M, TYNHN6C, 1, RIT1, SOS1 TAZ, TBX20, TTN MYTHN7N, IM3, Y PTNN,N NTE2X, N, RATFP1M, T1C, ATTPR, T, VNCNLC1, TNNI3, TNNT2, TPM1, TTR, VCL Comprehensive, Targeted and Lipid Panel Gene Lists ALL PANELS HAVE A TURNAROUND TIME OF 2-3 WEEKS CardioNext TAADNext NoonanNext FHNext 92 genes 35 genes 18 genes 4 genes + SNP ABCC9 LAMA4 ACTA2 BRAF APOB ACTC1 LAMP2 BGN CBL LDLR ACTN2 LDB3 CBS HRAS LDLRAP1 AKAP9 LMNA CHST14 KRAS PCSK9 ALMS1 MYBPC3 COL1A1 LZTR1 SLCO1B1 (c.521T>C)* ALPK3 MYH6 COL1A2 MAP2K1 ANK2 MYH7 COL3A1 MAP2K2 ANKRD1 MYL2 COL5A1 NF1 FCSNext BAG3 MYL3 COL5A2 NRAS 5 genes CACNA1C MYOZ2 EFEMP2 PPP1CB APOA5 CACNA2D1 MYPN FBN1 PTPN11 APOC2 CACNB2 NEXN FBN2 RAF1 GPIHBP1 CALM1 NKX2.5 FKBP14 RASA1 CALM2 PKP2 FLNA RIT1 LMF1 CALM3 PLN FOXE3 SHOC2 LPL CASQ2 PRKAG2 LOX SOS1 CAV3 PTPN11 MAT2A SOS2 Sitosterolemia CRYAB RAF1 MED12 SPRED1 CSRP3 RBM20 MFAP5 2 genes DES RIT1 MYH11 ABCG5 DMD RYR2 MYLK ABCG8 DOLK SCN10A NOTCH1 DSC2 SCN1B PLOD1 SCN2B CustomNext-Cardio DSG2 PRDM5 DSP SCN3B PRKG1 Up to 18 EMD SCN4B SKI additional lipid genes EYA4 SCN5A SLC2A10 ABCA1 FHL1 SNTA1 SMAD3 ABCG5 FKRP SOS1 SMAD4 ABCG8 FKTN TAZ TGFB2 APOA1 FLNC TBX20 TGFB3 GATAD1 TBX5 TGFBR1 APOA5 GLA TCAP TGFBR2 APOB GPD1L TECRL TNXB APOC2 HCN4 TGFB3 ZNF469 APOC3 JPH2 TMEM43 APOE JUP TNNC1 CYP27A1 KCND3 TNNI3 GPIHBP1 KCNE1 TNNT2 LCAT KCNE2 TPM1 LDLR KCNE3 TRDN LDLRAP1 KCNH2 TRPM4 KCNJ2 TTN LIPA KCNJ5 TTR LMF1 KCNJ8 TXNRD2 LPL KCNQ1 VCL PCSK9 CustomNext-Cardio allows you to choose your own combination of up to 167 genes. * Optional Over 1 Million Tests Completed moving science forward Free Family Member Testing Free testing for ALL family members is now available within 90 days of the original report if the proband was tested at Ambry. Family testing is done via specific site analysis for pathogenic or likely pathogenic variants. (Excludes SNP array and applies to single gene, panel or exome testing.) Purposeful Confirmatory Testing Many labs validate their tests based on certain limited studies. That’s why we led the largest study of its kind (20,000 cases) guiding us to utilize confirmatory testing when we see specific well-defined thresholds. Our mission is to get it right the first time. Flexible Sample Options Ambry accepts blood, saliva and other sample types to perform genetic testing. Sample for Life We periodically review variants and let you know when there is updated information, such as a reclassification. This is part of our commitment to finding answers. About Ambry Just as no two fingerprints are alike, the way disease presents itself in every individual is different. Since 1999, our mission has always been about understanding disease better, so treatments and cures can be found faster. Every sample that arrives in our lab is viewed as a person with a life and a story that is unique to only them. By providing advanced confirmation genetic testing for inherited and non-inherited diseases, we can help you make more informed and responsible medical management decisions with your patients. Visit ambrygen.com for more information. 50339.5460_v2 | 12.04.18 15 Argonaut, Aliso Viejo, CA 92656 USA Toll Free +1 866 262 7943 Fax +1 949 900 5501 ambrygen.com.
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  • Communication Pathways in Human Nonmuscle Myosin-2C 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Authors: 25 Krishna Chinthalapudia,B,C,1, Sarah M

    Communication Pathways in Human Nonmuscle Myosin-2C 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Authors: 25 Krishna Chinthalapudia,B,C,1, Sarah M

    1 Mechanistic Insights into the Active Site and Allosteric 2 Communication Pathways in Human Nonmuscle Myosin-2C 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Authors: 25 Krishna Chinthalapudia,b,c,1, Sarah M. Heisslera,d,1, Matthias Prellera,e, James R. Sellersd,2, and 26 Dietmar J. Mansteina,b,2 27 28 Author Affiliations 29 aInstitute for Biophysical Chemistry, OE4350 Hannover Medical School, 30625 Hannover, 30 Germany. 31 bDivision for Structural Biochemistry, OE8830, Hannover Medical School, 30625 Hannover, 32 Germany. 33 cCell Adhesion Laboratory, Department of Integrative Structural and Computational Biology, The 34 Scripps Research Institute, Jupiter, Florida 33458, USA. 35 dLaboratory of Molecular Physiology, NHLBI, National Institutes of Health, Bethesda, Maryland 36 20892, USA. 37 eCentre for Structural Systems Biology (CSSB), German Electron Synchrotron (DESY), 22607 38 Hamburg, Germany. 39 1K.C. and S.M.H. contributed equally to this work 40 2To whom correspondence may be addressed: E-mail: [email protected] or 41 [email protected] 42 43 1 44 Abstract 45 Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by 46 F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 Å crystal pre- 47 powerstroke state (ADPVO4) structure of the human nonmuscle myosin-2C motor domain, one 48 of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble- 49 solution kinetics, and molecular dynamics simulation approaches, the structure reveals an 50 allosteric communication pathway that connects the distal end of the motor domain with the 51 active site.