Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 1. Characterization of voltage-gated sodium currents in ovarian cancer cells. (A and B) Western blot analysis of Nav1.5 protein expression in the ovarian cancer cell lines SKOV3, A2780 and TOV112D (n=7). (C) Voltage‑gated sodium currents recorded in SKOV3, A2780 and TOV112D cells. Currents were activated by depolarization to -10 mV for 50 msec from a holding potential of -110 mV. (D) Sodium currents recorded in ovarian cancer cells prior to and following the addition of 10 µM TTX. (E) Dose-dependent effects of TTX on sodium current inhibition (n=5 for each concentration; data are presented as the means ± standard error of the mean), curves are Hill fits of the data points. TTX, tetrodotoxin.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Western Blot, Analysis, Expressing, Inhibition, Concentration Assay, Patch Clamp

Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 2. Effects of Nav1.5 knockdown on sodium currents in SKOV3 cells. (A and B) Western blot analysis of Nav1.5 expression in SKOV3 cells transfected with 40 nM SiCtl, or 20 or 40 nM SiNav1.5 (n=5). *P<0.05 vs. SiCtl. (C) Normalized I-V plot of currents recorded from cells in the various groups (control, 40 nM SiCtl and 40 nM SiNav1.5) (n=7 for each group; data are presented as the means ± standard error of the mean). (D) Examples of sodium currents in the control, SiCtl and SiNav1.5 cell groups. Currents were activated by depolarization to -10 mV with 50 msec duration from a holding potential of -110 mV. SiCtl, control siRNA; SiNav1.5 Nav1.5-specific siRNA; siRNA, small interfering RNA.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Knockdown, Western Blot, Analysis, Expressing, Transfection, Control, Small Interfering RNA, Patch Clamp

Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 4. Effects of EPA on steady-state inactivation and activation of the sodium currents in SKOV3 ovarian cancer cells. (A) Steady-state inactivation curve of sodium currents prior to and after treatment with 15 µM EPA. Currents were elicited to 0 mV following prepulses ranging between -140 and 0 mV in 10 mV steps for 200 msec (n=7; data are presented as the means ± standard error of the mean). (B) Steady-state activation curve of the Nav1.5 sodium channel prior to and after treatment with 15 µM EPA. Currents were measured from a holding potential of -110 mV to test potentials ranging between -110 and +70 mV in 10 mV steps (n=7; data are presented as the means ± standard error of the mean). (A and B) Curves are Boltzmann fits of the data points. (C) Steady-state activation and inactivation V1/2 prior to and after treatment with 15 µM EPA (n=7; data are presented as the means ± standard error of the mean). *P<0.05 vs. the control. (D) Plots of current availability by the Boltzmann fits of inactivation curve in (A) and activation curve in (B), gray dashed box indicates window currents. Right inset shows sodium window currents prior to treatment with EPA (control), left inset shows sodium window currents after treatment with 15 µM EPA. EPA, eicosapentaenoic acid.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Inactivation, Activation Assay, Control

Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 7. Effects of EPA on steady-state inactivation and activation of the Nav1.5 currents in 293T cells. (A) Steady-state inactivation curve of Nav1.5 currents prior to and after treatment with 5 µM EPA. Currents were elicited to 0 mV following prepulses ranging between -140 and 0 mV in 10 mV steps for 200 msec (n=6; data are presented as the means ± standard error of the mean). (B) Steady-state activation curve of the Nav1.5 sodium channel prior to and after treatment with 5 µM EPA. Currents were measured from a holding potential of -110 mV to test potentials ranging between -110 and +70 mV in 10 mV steps (n=6; data are presented as the means ± standard error of the mean). (A and B) Curves are Boltzmann fits of the data points. (C) Steady-state activation and inactivation V1/2 prior to and after treatment with 5 µM EPA (n=6; data are presented as the means ± standard error of the mean). *P<0.05 vs. the control. (D) Normalized I-V plot of Nav1.5 currents recorded from cells prior to and after treatment with 5 µM EPA (n=6; data are presented as the means ± standard error of the mean). EPA, eicosapentaenoic acid.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Inactivation, Activation Assay, Control

Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 9. Effects of EPA on SKOV3 cell proliferation. (A) EPA inhibited proliferation of SKOV3 cells in a dose-dependent manner (n=7 for each concentration; data are presented as the means ± standard error of the mean). Curves are Hill fits of the data points. (B) Effects of Nav1.5 siRNA on the inhibitory effects of 15 µM EPA on cell proliferation in SKOV3 cells (n=6; data are presented as the means ± standard error of the mean). *P<0.05 vs. the control, or as indicated. EPA, eicosapentaenoic acid; siRNA, small interfering RNA.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Concentration Assay, Control, Small Interfering RNA, Knockdown

Journal: International journal of oncology

Article Title: Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells.

doi: 10.3892/ijo.2018.4437

Figure Lengend Snippet: Figure 8. Inhibition of the Nav1.5 channel attenuates SKOV3 cell migration. (A) Representative images (magnification, x10) of in vitro wound healing at 36 h after creation of the wounds in cells treated with 40 nM SiNav1.5, 40 nM SiCtl, 200 µM EPA, or SiNav1.5 + 200 µM EPA. Images were captured under an inverted phase contrast microscope. (B) Bars indicate results shown in (A) (n=6 for each group; data are presented as the means ± standard error of the mean). *P<0.05 vs. the control and SiCtl. (C) EPA inhibited SKOV3 cell migration in a dose-dependent manner (n=7 for each concentration; data are presented as the means ± standard error of the mean). Curves are Hill fits of the data points. EPA, eicosapentaenoic acid; SiCtl, control siRNA; SiNav1.5 Nav1.5-specific siRNA; siRNA, small interfering RNA.

Article Snippet: Membranes were blocked at room temperature for 1 h in 5% non-fat milk dissolved in Tris-buffered saline containing Tween-20 (150 mM NaCl, 50 mM Tris, 0.1% Tween-20; pH 7.5), and were incubated with rabbit anti-human Nav1.5 (1:1,000, ASC-013; Alomone Labs, Jerusalem, Israel) and rabbit anti-GAPDH (1:1,000, #5174; Cell Signaling Technology, Inc., Danvers, MA, USA) primary antibodies at 4 ̊C overnight.

Techniques: Inhibition, Migration, In Vitro, Phase Contrast, Microscopy, Control, Concentration Assay, Small Interfering RNA

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 1. Human macrophage SCN5A splice variant associates with the transcription factor ATF2. To confirm the results from LC/MS (Table 1), immunoprecipitation (IP) of human SCN5A was performed in BMDM from transgenic and wild type conditions. BMDM from the transgenic mice express the human macrophage SCN5A variant under the control of a cfms promoter (24). Co-immunoprecipitation of ATF2 (red) was observed in the transgenic (TG) but not wild type (WT) condition. Difference gel electrophoresis labeling for total protein content in the lysate is shown in blue.

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Variant Assay, Liquid Chromatography with Mass Spectroscopy, Immunoprecipitation, Transgenic Assay, Control, Nucleic Acid Electrophoresis, Labeling

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 2. Pharmacological activation increases phospho-ATF2 levels. A, human SCN5A (hSCN5A) and wild type BMDM were treated with the sodium channel agonist, veratridine (100 M), for 15 min and then stained for total ATF2 (red), phospho-ATF2 (green), and DNA (DAPI, blue). Scale bar, 10 m. Quantitative analysis (AxioVision auto-measurement module) revealed a statistically significant difference in nuclear phospho-ATF2 staining between the two conditions (top micrographs). Fluorescent densitometric sum/nucleus was 5.58 106 0.71 106 in hSCN5A cells versus 0.32 106 0.14 106 in the wild type condition (p 0.01, n 4 cell samples; 46 cells analyzed for the hSCN5A condition and 54 cells for the wild type condition; S.E.). Baseline staining in the SCN5A BMDM without treatment is shown on the bottom. Scale bar, 10 m. B, Western blot analysis was performed to confirm phospho-ATF2 cell staining. Veratridine treatment of mouse BMDM for 15 min led to markedly increased phospho-ATF2 levels in transgenic human SCN5A (hSCN5A) macrophages (Tg) but not in the wild type conditions (WT) or following vehicle (DMSO) treatment. Densitometric analysis (ImageJ) revealed relative fluorescent units of 0.24 0.13 for vehicle-treated transgenic BMDM, 0.31 0.08 for vehicle-treated WT, 0.87 0.05 for veratridine-treated transgenic cells (p 0.01 ANOVA, n 4 cell preparations, S.E.), and 0.28 0.15 for veratridine-treated WT. TG, transgenic.

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Activation Assay, Staining, Western Blot, Transgenic Assay

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 5. SCN5A mediates a veratridine-induced calcium response in human monocyte-derived macrophages. Human MDM were labeled with the calcium indicator Fluo4 and imaged by time-lapse live cell microscopy. Stimulation of human MDM with veratridine (100 M) elicited a biphasic peak response and a more prolonged elevation in cytosolic calcium. The initial peak response (Peak 1) and the sustained response, but not Peak 2, were dependent on expression of SCN5A and RYR1. Images were acquired at 10-s intervals for 10 min and subsequently analyzed in ImageJ and MATLAB. The top graph shows representative tracings for each condition. The bar graphs show quantitative analysis of peak responses and the cumulative response (AUC, area under the curve). For peak 1, the mean responses were as follows: 80.2 5.8 RFUs for control siRNA, 15.1 4.9 for SCN5A knockdown, and 13.4 3.2 for RYR1 knockdown (p 0.001 for control condition, ANOVA, n 10 regions of interest, error bars, S.E.). For peak 2, 32.3 2.7 for control siRNA, 48.9 5.8 for SCN5A knockdown, and 31.7 5.1 for RYR1 knockdown (not significant, ANOVA, n 10). The AUC was 1909.0 163.1 for the siRNA con- trolcondition,803.3192.5forSCN5Aknockdown,and164.640.3forRYR1 knockdown (p 0.001 for control condition, ANOVA, n 10).

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Derivative Assay, Labeling, Microscopy, Expressing, Control, Knockdown

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 6. Pharmacological activation of human monocyte-derived macrophages regulates signal transduction and transcription that is dependent on SCN5A expression. A, veratridine treatment (100 M for 15 min) increased cAMP levels in human MDM in control siRNA conditions but not following knockdown of SCN5A, ADCY8, or RYR1 (Table 5). B, veratridine treatment (100 M for 2 h) increased Sp100 mRNA levels in control siRNA-treated MDM but not following SCN5A knockdown (Table 6). C, veratridine treatment (100 M for 2 h) markedly increased IFNB transcription in MDM treated with control siRNA. Knockdown of SCN5A, ADCY8, or ATF2 inhibited this response (Table 7). Error bars, S.E., from pooled replicates from a representative donor. Similar results were obtained from a second donor.

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Activation Assay, Derivative Assay, Transduction, Expressing, Control, Knockdown

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 7. Transfection of poly(I:C) complexes is similar in the presence or absence of macrophage SCN5A. The indicated cell types were challenged with rhodamine-labeled poly(I:C) (LMW, 200 nM for 20 min) and subsequently washed and fixed for microscopic analysis (scale bars, 20 m).

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Transfection, Labeling

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 8. Poly(I:C) treatment initiates SCN5A-dependent transcription. A, in mouse BMDM that express the human macrophage SCN5A variant, transfection of poly(I:C) (low molecular weight, 200 ng/ml for 2 h), but not treatment with naked poly(I:C) (200 ng/ml for 2 h), increased expression of Gm7609 transcripts. This increase was not observed in wild type, SCN5A-negative cells, or in transgenic cells following siRNA knockdown of Adcy8 or ATF2 (Table 8) (error bars, S.E. from pooled replicates of multiple RNA preparations). B, in human MDM treated with control siRNA, increased transcription of IFNB was observed following treatment with transfected poly(I:C) (200 ng/ml for 2 h). This increase was inhibited by siRNA knockdown of SCN5A or ATF2; knockdown of DDX58 (RIG-1) also reduced the response but to a lesser degree (Table 9). Error bars, S.E., from pooled replicates from a representative donor. Similar results were obtained from a second donor. C, knockdown of MyD88 or TRIF (TICAM-1) increased expression of IFNB in response to cytosolic poly(I:C) in human MDM (Table 10). D, human MDM were infected with HSV-1 for 24 h, and transcription of viral transcripts glycoprotein B (GB) and thymidine kinase (TK) was analyzed. Knockdown of SCN5A, but not treatment with control siRNA, increased transcription of glycoprotein B and thymidine kinase (Table 11).

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Variant Assay, Transfection, Molecular Weight, Expressing, Transgenic Assay, Knockdown, Control, Infection

Journal: Journal of Biological Chemistry

Article Title: Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense

doi: 10.1074/jbc.m114.611962

Figure Lengend Snippet: FIGURE 9. Poly(I:C) increases cAMP levels and currents in HEK-293 cells that heterologously express human macrophage SCN5A. A, cAMP levels were monitored by live cell imaging using the cyclic nucleotide-gated channel assay (Fig. 4). Poly(I:C) treatment (low molecular weight, 200 ng/ml) increased cAMP levels 10 and 15 min post-challenge in SCN5A-transfected cells but not mock-transfected HEK-293 cells. Normalized fluorescent ratios were 1.39 0.13 (5 min), 2.42 0.32 (10 min), and 2.44 0.32 (15 min) for the SCN5A condition and 1.15 0.10 (5 min), 1.02 0.17 (10 min), and 1.24 0.11 (15 min) for the control condition (error bars, S.E., n 10 regions of interest for each condition, p 0.05 for 10 and 15 min conditions). B, whole cell patch clamp analysis revealed outward and inward currents in SCN5A-expressing cells with cesium (Cs) as the predominant intracellular cation and sodium in the extracellular solution (second recording from top). Outward currents were reduced in control transfected cells (top current recording), and an inward current was not seen. Poly(I:C) in the intracellular solution (200 ng/ml; third from top) markedly increased a voltage-dependent inward current in SCN5A-positive cells and reduced the outward current. Replacement of sodium (Na) with NMDG in the extracellular solution (bottom current recording) prevented the poly(I:C) induced inward current. C, I-V curve analysis of the experiments shown in B. Ambroxol (50 M), an inhibitor of tetrodotoxin-resistant sodium channels, reduced inward but not outward currents in SCN5A cells. Data in Tables 12–15 show statistical analysis of currents at 40 mV and 20 mV in the absence and presence of intracellular poly(I:C). Data are pooled, and normalized (pA/picofarad (pF)) current recordings and are expressed as S.D.

Article Snippet: The following TaqMan primers were obtained from Applied Biosystems/Invitrogen: Hs00165693_m1 (human SCN5A), Mm99999915_g1 (mouse Gapdh), Mm00449735_m1 (mouse Sp100), Mm04204797_m1 (mouseGm7609),Hs00162109_m1(humanSP100),Hs01077958_ s1 (human IFNB1), AIGJQ71 (HSV thymidine kinase), and AIHSPDQ (HSV glycoprotein B (8)).

Techniques: Live Cell Imaging, Molecular Weight, Transfection, Control, Patch Clamp, Expressing

Journal: Nature reviews. Disease primers

Article Title: Inherited cardiac arrhythmias

doi: 10.1038/s41572-020-0188-7

Figure Lengend Snippet: Genes frequently associated with inherited cardiac arrhythmias

Article Snippet: Furthermore, the recent reappraisal of all reported BrS susceptibility genes (either by testing for an increased burden of rare genetic variants in patients with BrS compared with controls 65 or by the application of the ClinGen evidence-based gene curation framework 64 ) supports only the involvement of rare variations in SCN5A , which are found in ~20% of probands 65 .

Techniques: Membrane

Journal: Current opinion in genetics & development

Article Title: Genetics of Congenital Arrhythmia Syndromes: The Challenge of Variant Interpretation

doi: 10.1016/j.gde.2022.102004

Figure Lengend Snippet: ClinGen reappraisal of genes associated with inherited arrhythmia syndromes

Article Snippet: Table 1: ClinGen Class Long QT syndrome Brugada syndrome Catecholaminergic polymorphic VT Short QT syndrome Other Definitive KCNQ1, KCNH2, SCN5A, CALM1/2/3 SCN5A RYR2, CASQ2 (AR) , TRDN, TECRL KCNH2 CACNA1C (Timothy), KCNJ2 (Anderson-Tawil) Strong TRDN (AR) — — KCNQ1, SLC4A3 * KCNE1 (aLQTS), KCNE2 (aLQTS) Moderate CACNA1C — CASQ2(AD), CALM1/2/3 SLC4A3 * , KCNJ2 — Limited CAV3, KCNE1, KCNJ2 — — — — Disputed/ No evidence SNTA1, AKAP9, ANK2, KCNE2, KCNJ5, SCN4B 20 genes ANK2, KCNJ2, PKP2, SCN5A CACNA1C, CACNA2D1, CACNB2, SCN5A, SLC22A5 ** — Open in a separate window Adapted from ClinGen reappraisals of LQTS [ 4 ], BrS [ 5 ], and CPVT/SQTS [ 6 ].

Techniques:

Journal: Current opinion in genetics & development

Article Title: Genetics of Congenital Arrhythmia Syndromes: The Challenge of Variant Interpretation

doi: 10.1016/j.gde.2022.102004

Figure Lengend Snippet: ClinGen reappraisal of genes associated with inherited arrhythmia syndromes

Article Snippet: Table 1: ClinGen Class Long QT syndrome Brugada syndrome Catecholaminergic polymorphic VT Short QT syndrome Other Definitive KCNQ1, KCNH2, SCN5A, CALM1/2/3 SCN5A RYR2, CASQ2 (AR) , TRDN, TECRL KCNH2 CACNA1C (Timothy), KCNJ2 (Anderson-Tawil) Strong TRDN (AR) — — KCNQ1, SLC4A3 * KCNE1 (aLQTS), KCNE2 (aLQTS) Moderate CACNA1C — CASQ2(AD), CALM1/2/3 SLC4A3 * , KCNJ2 — Limited CAV3, KCNE1, KCNJ2 — — — — Disputed/ No evidence SNTA1, AKAP9, ANK2, KCNE2, KCNJ5, SCN4B 20 genes ANK2, KCNJ2, PKP2, SCN5A CACNA1C, CACNA2D1, CACNB2, SCN5A, SLC22A5 ** — Open in a separate window Adapted from ClinGen reappraisals of LQTS [ 4 ], BrS [ 5 ], and CPVT/SQTS [ 6 ].

Techniques:

Journal: Current opinion in genetics & development

Article Title: Genetics of Congenital Arrhythmia Syndromes: The Challenge of Variant Interpretation

doi: 10.1016/j.gde.2022.102004

Figure Lengend Snippet: ClinGen reappraisal of genes associated with inherited arrhythmia syndromes

Article Snippet: Table 1: ClinGen Class Long QT syndrome Brugada syndrome Catecholaminergic polymorphic VT Short QT syndrome Other Definitive KCNQ1, KCNH2, SCN5A, CALM1/2/3 SCN5A RYR2, CASQ2 (AR) , TRDN, TECRL KCNH2 CACNA1C (Timothy), KCNJ2 (Anderson-Tawil) Strong TRDN (AR) — — KCNQ1, SLC4A3 * KCNE1 (aLQTS), KCNE2 (aLQTS) Moderate CACNA1C — CASQ2(AD), CALM1/2/3 SLC4A3 * , KCNJ2 — Limited CAV3, KCNE1, KCNJ2 — — — — Disputed/ No evidence SNTA1, AKAP9, ANK2, KCNE2, KCNJ5, SCN4B 20 genes ANK2, KCNJ2, PKP2, SCN5A CACNA1C, CACNA2D1, CACNB2, SCN5A, SLC22A5 ** — Open in a separate window Adapted from ClinGen reappraisals of LQTS [ 4 ], BrS [ 5 ], and CPVT/SQTS [ 6 ].

Techniques: