- Mar 2021
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 6.6
AssayResultAssertion: Normal
StandardErrorMean: 0.05
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 6.6
AssayResultAssertion: Normal
StandardErrorMean: 0.8
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 6.9
AssayResultAssertion: Normal
StandardErrorMean: 0.35
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.1
AssayResultAssertion: Normal
StandardErrorMean: 0.43
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.2
AssayResultAssertion: Normal
StandardErrorMean: 0.01
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.3
AssayResultAssertion: Normal
StandardErrorMean: 0.08
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.5
AssayResultAssertion: Normal
StandardErrorMean: 0.61
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.7
AssayResultAssertion: Normal
StandardErrorMean: 0.15
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Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
AssayResult: 7.7
AssayResultAssertion: Normal
StandardErrorMean: 0.15
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A total of 84 PALB2 patient-derived missense variants reported in ClinVar, COSMIC, and the PALB2 LOVD database were selected
HGVS: NM_024675.3:c.100C>T p.(Arg34Cys)
Tags
- CAID:CA166841
- CGType:Variant
- ClinVarID:185273
- Variant:61
- CAID:CA288398
- ClinVarID:126591
- Variant:14
- ClinVarID:126731
- CAID:CA269610
- Variant:71
- ClinVarID:126595
- ClinVarID:141936
- Variant:62
- Variant:25
- CAID:CA299799
- CAID:CA288475
- CAID:CA288441
- Variant:1
- Variant:73
- CAID:CA269483
- CAID:CA269619
- CGType:FunctionalAssayResult
- Variant:8
- ClinVarID:126647
- Variant:28
- CAID:CA191499
- Variant:29
- CAID:CA288435
- ClinVarID:126741
- ClinVarID:126640
- ClinVarID:126732
- ClinVarID:126652
- FuncAssay:1
- CG:BulkAnnotation
Annotators
URL
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Olaparib sensitivity assayFor the sensitivity assay in HeLa, 240 000 cells were seeded into one well of a six-well plate before being transfected 6–8 h later with 50 nM control or PALB2 siRNA using Lipofectamine RNAiMAX (Invitrogen). The next morning, cells were complemented with 800 ng of the peYFP-C1 empty vector or the indicated siRNA-resistant YFP-tagged PALB2 construct using Lipofectamine 2000 (Invitrogen) for 24 h and then seeded in triplicates into a Corning 3603 black-sided clear bottom 96-well microplate at a density of 3000 cells per well. The remaining cells were kept and stored at −80°C until processed for protein extraction and immunoblotting as described above. Once attached to the plate, cells were exposed to different concentrations of olaparib (Selleckchem, #S1060) ranging from 0 (DMSO) to 2.5 μM. After 3 days of treatment, nuclei were stained with Hoechst 33342 (Invitrogen) at 10 μg/ml in media for 45 min at 37°C. Images of entire wells were acquired at 4x with a Cytation 5 Cell Imaging Multi-Mode Reader followed by quantification of Hoechst-stained nuclei with the Gen5 Data Analysis Software v3.03 (BioTek Instruments). Cell viability was expressed as percentage of survival in olaparib-treated cells relative to vehicle (DMSO)-treated cells. Results represent the mean ± SD of at least 3 independent experiments, each performed in triplicate.
AssayGeneralClass: BAO:0003009 cell viability assay
AssayMaterialUsed: CLO:0003684 HeLa cell
AssayDescription: HeLa cells were treated with PALB2 siRNA followed by transfection peYFP-PALB2 expressing PALB2 variants (or empty vector) and exposed to olaparib (2.5 µM) for 3 days. Nuclei were stained with Hoechst 33342 and measured as an indicator of cell viability.
AssayReadOutDescription: Cell viability expressed as percentage of survival in olaparib-treated cells relative to vehicle (DMSO)-treated cells
AssayRange: %
AssayNormalRange: Not reported
AssayAbnormalRange: Not reported
AssayIndeterminateRange: Not reported
ValidationControlPathogenic: 1
ValidationControlBenign: 3
Replication: At least 3 independent experiments, each performed in triplicate
StatisticalAnalysisDescription: Kruskal–Wallis test with Dunn's multiple comparison post-test
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SUPPLEMENTARY DATA
AssayResult: 5
AssayResultAssertion: Abnormal
PValue: < 0.0001
Approximation: Exact assay result value not reported; value estimated from Figure 6C.
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SUPPLEMENTARY DATA
AssayResult: -98
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: 48
AssayResultAssertion: Abnormal
PValue: < 0.0001
Approximation: Exact assay result value not reported; value estimated from Figure 1D.
ControlType: Abnormal; empty vector
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SUPPLEMENTARY DATA
AssayResult: 100
AssayResultAssertion: Normal
ControlType: Normal; wild type PALB2 cDNA
-
SUPPLEMENTARY DATA
AssayResult: 106
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 108.6
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 64.45
AssayResultAssertion: Abnormal
PValue: < 0.0001
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 84.49
AssayResultAssertion: Indeterminate
PValue: 0.0058
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 92.43
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 88.66
AssayResultAssertion: Not reported
PValue: 0.727
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 96.63
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 97.59
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 94.36
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 98.94
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 87.19
AssayResultAssertion: Not reported
PValue: 0.341
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 98.25
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 57.61
AssayResultAssertion: Abnormal
PValue: < 0.0001
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 109.2
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 95.47
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 97.77
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 103.5
AssayResultAssertion: Normal
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 100.7
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 102.6
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 77.32
AssayResultAssertion: Indeterminate
PValue: 0.0002
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 82.22
AssayResultAssertion: Indeterminate
PValue: 0.004
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 96.97
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 102.1
AssayResultAssertion: Normal
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 101.6
AssayResultAssertion: Normal
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 109.7
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 109.4
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 107.5
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 100.5
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 103.3
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 108.7
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 106.8
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 94.01
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 92.68
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 92.03
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 93.06
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 86.49
AssayResultAssertion: Not reported
PValue: 0.3376
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 76.21
AssayResultAssertion: Indeterminate
PValue: 0.0001
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 85.76
AssayResultAssertion: Indeterminate
PValue: 0.0445
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 47.64
AssayResultAssertion: Abnormal
PValue: < 0.0001
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 86.51
AssayResultAssertion: Not reported
PValue: 0.2166
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 97.46
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 91.53
AssayResultAssertion: Not reported
PValue: > 0.9999
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 82.06
AssayResultAssertion: Indeterminate
PValue: 0.0058
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 76.45
AssayResultAssertion: Indeterminate
PValue: 0.0001
Comment: Exact values reported in Table S3.
-
SUPPLEMENTARY DATA
AssayResult: 86.74
AssayResultAssertion: Not reported
PValue: 0.1836
Comment: Exact values reported in Table S3.
-
To this end, 44 missense variants found in breast cancer patients were identified in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar) and/or selected by literature curation based on their frequency of description or amino acid substitution position in the protein (Supplemental Table S1).
HGVS: NM_024675.3:c.104T>C p.(Leu35Pro)
Tags
- Variant:10
- ClinVarID:126774
- ClinVarID:657666
- CAID:CA294183
- ClinVarID:126727
- Variant:40
- Variant:41
- AssayRangeType:Quantitative
- ClinVarID:126758
- CAID:CA193686
- ValidationControl:Benign
- Variant:25
- Variant:13
- CAID:CA395139336
- CAID:CA299799
- Variant:1
- Variant:34
- ClinVarID:126779
- Variant:26
- CAID:CA7963442
- CAID:CA395139432
- Variant:7
- ClinVarID:126743
- ClinVarID:582957
- CAID:CA395140053
- ClinVarID:126593
- ClinVarID:126741
- CAID:CA348162
- Variant:16
- CGType:Variant
- FuncAssay:1
- Variant:44
- CAID:CA161333
- ClinVarID:241553
- Variant:11
- ClinVarID:126682
- CAID:CA269654
- CAID:CA288504
- AssayControl:Abnormal
- CAID:CA161318
- CAID:CA395144524
- CAID:CA151239
- HGNC:26144
- CAID:CA331799
- ClinVarID:128150
- Variant:6
- Variant:4
- FuncAssay:2
- Variant:15
- Variant:30
- CGType:FunctionalAssayResult
- CAID:CA239946
- ClinVarID:126590
- ClinVarID:657328
- CAID:CA7963465
- CAID:CA269663
- CAID:CA168501
- ClinVarID:126652
- CG:BulkAnnotation
- CAID:CA395139263
- Variant:23
- CAID:CA279500276
- CAID:CA196624
- CAID:CA269585
- CAID:CA186642
- Variant:14
- CAID:CA151242
- CAID:CA279502031
- Variant:36
- CAID:CA288392
- ClinVarID:126781
- Variant:31
- CAID:CA331796
- Variant:27
- CAID:CA334766
- ClinVarID:126755
- CAID:CA288441
- ClinVarID:183828
- CAID:CA277851
- ClinVarID:126760
- CAID:CA161321
- CAID:CA299750
- Variant:28
- ClinVarID:187058
- Variant:29
- Variant:22
- ClinVarID:188387
- Variant:39
- Variant:37
- CAID:CA279500159
- CLO:0003684
- ClinVarID:182774
- MONDO:0016419
- AssayControl:Normal
- CAID:CA151236
- Variant:35
- Variant:20
- Variant:21
- ClinVarID:126761
- Variant:33
- Variant:17
- ClinVarID:126782
- CAID:CA269636
- Variant:18
- Variant:45
- Variant:12
- CAID:CA288386
- ClinVarID:126747
- ClinVarID:126669
- Variant:38
- Variant:32
- ValidationControl:WildType
- Variant:9
- Variant:3
- CAID:CA7963418
- ClinVarID:126699
- ClinVarID:217917
- ValidationControl:Pathogenic
- ClinVarID:487020
- CAID:CA269625
- CAID:CA161315
- BAO:0003009
- ClinVarID:126716
- Variant:5
- FuncAssay:3
- Variant:24
- ClinVarID:232977
- Variant:19
- CGType:FunctionalAssay
- ClinVarID:422560
- CAID:CA269666
- CAID:CA269619
- Variant:43
- Variant:2
- ClinVarID:126683
- ClinVarID:126647
- ClinVarID:126708
- ClinVarID:128124
- ClinVarID:126693
- Variant:8
- CAID:CA10579934
- ClinVarID:220168
- ClinVarID:126731
- CAID:CA151233
- Variant:42
- ClinVarID:126738
- CAID:CA269610
- UO:0000187
Annotators
URL
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www.biorxiv.org www.biorxiv.org
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Reviewer #1 (Public Review):
The authors used a CRISPR screen to investigate the basis of metastasis of ovarian cancer (OC) cells. Overall, they identified two key genes, IL20RA, one of which was studied in detail. They identify an IL20/IL20RA communication between ovarian cancer cells and peritoneal mesothelial cells to promote M1 macrophages and prevent dissemination of the cancer cells. IL-20 mediated crosstalk is blocked in metastasized OC cells by decreased expression of IL-20RA. Interestingly, IL20RA is also decreased in cells from OC patients with peritoneal metastasis, and reconstitution of IL20RA in metastatic OC cells suppresses metastasis. Moreover, OC cells induce mesothelial cells to produce IL20 and IL24.
Overall, this is a nice study. It is well-written, and the data are clear. A range of methodologies are used that support the conclusions, with both over-expression and under-expression related studies supporting some key conclusions.
The overall model is that there is crosstalk between disseminated OC cells and mesothelial cells and macrophages. OC cells when disseminated into the peritoneal cavity stimulate mesothelial cells to produced IL20 and IL24, which via IL20RA trigger STAT3 to produced OAS/RNase L and production of IL-18, to promote an M1 phenotype. The M1 phenotype lowers metastasis. Highly metastatic cells block this pathway by decreasing IL20RA expression.
These findings are interesting, with potential therapeutic ramifications.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A cell-based functional assay for PALB2 variants
AssayGeneralClass: BAO:0003061 reporter protein
AssayMaterialUsed: CLO:0037317 mouse embryonic stem cell line
AssayDescription: Stable expression of wild type and variant PALB2 cDNA constructs in Trp53 and Palb2-null mouse cell line containing DR-GFP reporter; I-SceI endonuclease introduces a double-stranded break in the reporter construct and efficient repair results in GFP expression, which is detected by flow cytometry
AssayReadOutDescription: Relative homologous recombination (HR) efficiency represented as mean percentages of GFP-positive cells among the mCherry-positive cells relative to wild type, which was set to 100%
AssayRange: %
AssayNormalRange: HR levels comparable to that of cells expressing wild type PALB2; no numeric threshold given
AssayAbnormalRange: HR levels ≤40% of wild type
AssayIndeterminateRange: Not reported
ValidationControlPathogenic: 12
ValidationControlBenign: 9
Replication: 2 independent experiments
StatisticalAnalysisDescription: Not reported
-
Source Data
AssayResult: 115.71
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 3.09
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 80.95
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 0.01
StandardErrorMean: 0
Comment: Exact values reported in “Source Data” file. Discrepancy in “Supplementary Data 1” file: nucleotide reported as c.3191A>G.
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Source Data
AssayResult: 101.02
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.45
StandardErrorMean: 3.86
Comment: Exact values reported in “Source Data” file. Discrepancy in “Source Data” file: protein reported as T1064C.
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Source Data
AssayResult: 84.43
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.77
StandardErrorMean: 1.96
Comment: Exact values reported in “Source Data” file. Discrepancy in “Source Data” file: protein reported as L855P (based on matching values reported in the “Supplementary Data 1” file to values reported in the “Source Data” file.
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Source Data
AssayResult: 15.58
AssayResultAssertion: Abnormal
ReplicateCount: 6
StandardDeviation: 0.52
StandardErrorMean: 0.37
ControlType: Abnormal; empty vector (set 5)
Comment: Exact values reported in “Source Data” file.
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Source Data
AssayResult: 7.93
AssayResultAssertion: Abnormal
ReplicateCount: 6
StandardDeviation: 0.56
StandardErrorMean: 0.39
ControlType: Abnormal; empty vector (set 4)
Comment: Exact values reported in “Source Data” file.
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Source Data
AssayResult: 8.71
AssayResultAssertion: Abnormal
ReplicateCount: 6
StandardDeviation: 1.75
StandardErrorMean: 1.24
ControlType: Abnormal; empty vector (set 3)
Comment: Exact values reported in “Source Data” file.
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Source Data
AssayResult: 7.11
AssayResultAssertion: Abnormal
ReplicateCount: 6
StandardDeviation: 2.37
StandardErrorMean: 1.68
ControlType: Abnormal; empty vector (set 2)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.83
AssayResultAssertion: Abnormal
ReplicateCount: 6
StandardDeviation: 1.13
StandardErrorMean: 0.8
ControlType: Abnormal; empty vector (set 1)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 100
AssayResultAssertion: Normal
ReplicateCount: 38
StandardDeviation: 0
StandardErrorMean: 0
ControlType: Normal; wild type PALB2 cDNA
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 97.16
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 1.32
StandardErrorMean: 0.93
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 30.35
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 3.64
StandardErrorMean: 2.57
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 20.32
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.49
StandardErrorMean: 0.35
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.42
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.87
StandardErrorMean: 2.03
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 91.47
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 8.63
StandardErrorMean: 6.1
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 100.19
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.64
StandardErrorMean: 3.99
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.53
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.79
StandardErrorMean: 1.97
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 90.64
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 1.82
StandardErrorMean: 1.29
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 11.37
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.36
StandardErrorMean: 0.26
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 70.86
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 17.18
StandardErrorMean: 12.15
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 81.81
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 7.45
StandardErrorMean: 5.27
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 90.54
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 10.24
StandardErrorMean: 7.24
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 13.45
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.2
StandardErrorMean: 1.55
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 92.2
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 19.94
StandardErrorMean: 14.1
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 90.79
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 6.38
StandardErrorMean: 4.51
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 69.83
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.94
StandardErrorMean: 4.2
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 75.85
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 4.78
StandardErrorMean: 3.38
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 94.33
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 9.99
StandardErrorMean: 7.07
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 102.58
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.19
StandardErrorMean: 1.55
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 21.79
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.84
StandardErrorMean: 1.3
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 95.86
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 1.62
StandardErrorMean: 1.15
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 91.21
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 7.32
StandardErrorMean: 5.18
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.59
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.6
StandardErrorMean: 0.43
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 76.97
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 3.1
StandardErrorMean: 2.19
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.92
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.32
StandardErrorMean: 0.94
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 38.85
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 3.05
StandardErrorMean: 2.15
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 16.89
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 3.12
StandardErrorMean: 2.21
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 17.62
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.76
StandardErrorMean: 1.25
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 86.41
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 17.62
StandardErrorMean: 12.46
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 6.16
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.27
StandardErrorMean: 0.9
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 95.16
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardDeviation: 16.94
StandardErrorMean: 9.78
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.08
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.54
StandardErrorMean: 0.38
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 14.01
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.53
StandardErrorMean: 0.38
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 74.49
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.29
StandardErrorMean: 1.62
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 6.53
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.29
StandardErrorMean: 0.21
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 30.27
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.04
StandardErrorMean: 0.74
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.63
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.51
StandardErrorMean: 0.36
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 63.4
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.92
StandardErrorMean: 4.18
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 60.28
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardDeviation: 0.14
StandardErrorMean: 0.1
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 17.35
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 6.21
StandardErrorMean: 4.39
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 106.23
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 14.57
StandardErrorMean: 10.3
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 75.71
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 22.31
StandardErrorMean: 15.77
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 6.66
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 0.28
StandardErrorMean: 0.2
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 6.1
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.11
StandardErrorMean: 1.49
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 84.07
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.47
StandardErrorMean: 1.75
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 100.07
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 6.18
StandardErrorMean: 4.37
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 91.6
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 8.2
StandardErrorMean: 5.8
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 82.83
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 4.82
StandardErrorMean: 3.41
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 87.35
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 11.94
StandardErrorMean: 8.44
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 83.25
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.27
StandardErrorMean: 3.73
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.03
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.68
StandardErrorMean: 1.9
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 77.45
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 6.2
StandardErrorMean: 4.38
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 9.92
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.93
StandardErrorMean: 1.37
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 95.02
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 0.08
StandardErrorMean: 0.06
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.4
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 3.22
StandardErrorMean: 2.28
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.75
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.59
StandardErrorMean: 1.83
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 75.45
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 4.03
StandardErrorMean: 2.85
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 98.55
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 5.74
StandardErrorMean: 4.06
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 62.31
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 11.49
StandardErrorMean: 8.13
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 66.19
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 21.26
StandardErrorMean: 15.03
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 105.41
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 9.45
StandardErrorMean: 6.68
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.82
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 2.31
StandardErrorMean: 1.64
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 92.32
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.26
StandardErrorMean: 1.6
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 44.9
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 9.75
StandardErrorMean: 6.89
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 97.61
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 0.97
StandardErrorMean: 0.68
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 11.28
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardDeviation: 1.24
StandardErrorMean: 0.87
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 86.67
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardDeviation: 2.24
StandardErrorMean: 1.58
Comment: Exact values reported in “Source Data” file.
-
We, therefore, analyzed the effect of 48 PALB2 VUS (Fig. 2a, blue) and one synthetic missense variant (p.A1025R) (Fig. 2a, purple)29 on PALB2 function in HR.
HGVS: NM_024675.3:c.1010T>C p.(L337S)
Tags
- CAID:CA10580054
- CAID:CA395141224
- Variant:58
- ClinVarID:187262
- ClinVarID:1245
- AssayRangeType:Quantitative
- ClinVarID:126758
- ClinVarID:229718
- CAID:CA395141474
- ClinVarID:420826
- Variant:1
- ClinVarID:126613
- Variant:26
- CAID:CA192169
- Variant:50
- Variant:55
- Variant:47
- CAID:CA395144862
- CAID:CA250432
- FuncAssay:1
- Variant:44
- ClinVarID:142079
- ClinVarID:126711
- CAID:CA923726356
- ClinVarID:182741
- Variant:57
- CAID:CA151239
- Variant:6
- ClinVarID:530038
- CAID:CA395137656
- CAID:CA395121845
- ClinVarID:126706
- Variant:15
- CAID:CA163908
- Variant:30
- CGType:FunctionalAssayResult
- CAID:CA151222
- ClinVarID:657328
- CAID:CA7963465
- CAID:CA167348
- ClinVarID:134994
- ClinVarID:126594
- Variant:23
- ClinVarID:484164
- ClinVarID:186939
- CAID:CA294407
- CAID:CA151242
- ClinVarID:546043
- ClinVarID:185518
- CAID:CA279502031
- ClinVarID:126595
- ClinVarID:142468
- Variant:63
- ClinVarID:126600
- CAID:CA185966
- Variant:56
- Variant:31
- CAID:CA395144928
- ClinVarID:1246
- Variant:28
- Variant:46
- Variant:37
- CAID:CA339433
- ClinVarID:567901
- Variant:54
- AssayControl:Normal
- ClinVarID:484186
- Variant:35
- Variant:20
- ClinVarID:126623
- Variant:17
- Variant:65
- Variant:18
- Variant:45
- Variant:12
- CAID:CA288386
- Variant:3
- Variant:32
- CLO:0037317
- Variant:9
- CAID:CA196017
- ClinVarID:126699
- CAID:CA161315
- CAID:CA269625
- ClinVarID:232977
- Variant:19
- CAID:CA395139401
- Variant:43
- CAID:CA395141313
- Variant:8
- ClinVarID:126683
- ClinVarID:460996
- Variant:48
- CAID:CA151233
- Variant:61
- Variant:42
- CAID:CA251717
- Variant:10
- Variant:69
- ClinVarID:126774
- CAID:CA288398
- Variant:60
- ClinVarID:219647
- Variant:41
- Variant:40
- CAID:CA279530867
- ClinVarID:128136
- CAID:CA395139673
- CAID:CA10579985
- CAID:CA161327
- ValidationControl:Benign
- Variant:25
- Variant:13
- ClinVarID:126609
- Variant:51
- Variant:59
- Variant:34
- Variant:7
- ClinVarID:182773
- CAID:CA395145110
- CAID:CA251004
- CAID:CA395137985
- CAID:CA299663
- Variant:16
- ClinVarID:186824
- CGType:Variant
- CAID:CA16620118
- CAID:CA294562
- CAID:CA161333
- ClinVarID:241553
- CAID:CA269654
- CAID:CA658658444
- Variant:11
- ClinVarID:126582
- CAID:CA151229
- AssayControl:Abnormal
- Variant:52
- ClinVarID:126670
- CAID:CA164468
- HGNC:26144
- ClinVarID:461007
- ClinVarID:1243
- CAID:CA395142764
- Variant:4
- FuncAssay:2
- ClinVarID:186840
- CAID:CA163622
- Variant:68
- ClinVarID:126749
- CAID:CA269551
- ClinVarID:126590
- ClinVarID:216752
- CAID:CA7963653
- ClinVarID:126740
- CAID:CA299784
- ClinVarID:484219
- ClinVarID:126630
- CAID:CA395122261
- CG:BulkAnnotation
- CAID:CA161342
- CAID:CA279524947
- ClinVarID:126607
- Variant:14
- CAID:CA288478
- Variant:36
- Variant:64
- CAID:CA196291
- Variant:62
- Variant:49
- CAID:CA299747
- CAID:CA350039
- ClinVarID:922719
- CAID:CA16621924
- CAID:CA331796
- Variant:27
- CAID:CA151250
- Variant:29
- Variant:22
- Variant:39
- BAO:0003061
- Variant:67
- CAID:CA395137855
- MONDO:0016419
- CAID:CA151230
- ClinVarID:126761
- Variant:21
- Variant:66
- Variant:33
- Variant:38
- ClinVarID:126747
- ClinVarID:126669
- CAID:CA395144208
- ValidationControl:WildType
- CAID:CA494163316
- Variant:53
- ValidationControl:Pathogenic
- CAID:CA151212
- CAID:CA195974
- ClinVarID:182790
- ClinVarID:182786
- CAID:CA395125757
- ClinVarID:230588
- CAID:CA197176
- Variant:70
- Variant:24
- CGType:FunctionalAssay
- CAID:CA269492
- Variant:5
- Variant:2
- CAID:CA210470
- CAID:CA10579934
- ClinVarID:126738
- UO:0000187
Annotators
URL
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-
www.cell.com www.cell.com
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Automated Patch ClampingCells were patch clamped with the SyncroPatch 384PE automated patch clamping device (Nanion). To prepare cells for patch clamping, cells were washed in PBS, treated with Accutase (Millipore-Sigma) for 3 min at 37°C, then recovered in CHO-S-serum free media (GIBCO). Cells were pelleted and resuspended in divalent-free reference solution (DVF) at ∼200,000–400,000 cells/mL. DVF contained (mM) NaCl 140, KCl 4, alpha-D(+)-glucose 5, HEPES 10 (pH 7.4) adjusted with NaOH. Cells were then added to a medium resistance (4–6 MΩ) 384-well recording chamber with 1 patch aperture per well (NPC-384, Nanion), which contained DVF and internal solution: CsCl 10, NaCl 10, CsF 110, EGTA 10, HEPES 10 (pH 7.2) adjusted with CsOH. Next, to enhance seal resistance, 50% of the DVF was exchanged with a calcium-containing seal enhancing solution: NaCl 80, NMDG 60, KCl 4, MgCl2 1, CaCl2 10, alpha-D(+)-glucose 5, HEPES 10 (pH 7.4) adjusted with HCl. The cells were washed three times in external recording solution: NaCl 80, NMDG 60, KCl 4, MgCl2 1, CaCl2 2, alpha-D(+)-glucose 5, HEPES 10 (pH 7.4) adjusted with HCl. Currents elicited in response to activation, inactivation, and recovery from inactivation protocols were then recorded (Figure S2). A late current measurement was captured every 5 s. After 1 min, 50% of the external solution was exchanged with external solution containing 200 μM tetracaine hydrochloride (Sigma; effective concentration 100 μM tetracaine). After tetracaine addition, late current measurements were obtained every 5 s for 1 additional minute. At least 10 cells expressing wild-type SCN5A were included for comparison in each SyncroPatch experiment (Figure 1), and at least 2 independent transfections and at least 10 replicate cells were studied per mutant. Recordings were performed at room temperature.We also conducted experiments to assess the effects of incubation at low temperature or mexiletine (a sodium channel blocker), interventions reported to increase cell surface expression of mistrafficked channels.27Clatot J. Ziyadeh-Isleem A. Maugenre S. Denjoy I. Liu H. Dilanian G. Hatem S.N. Deschênes I. Coulombe A. Guicheney P. Neyroud N. Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 α-subunits.Cardiovasc. Res. 2012; 96: 53-63Crossref PubMed Scopus (62) Google Scholar, 28Makiyama T. Akao M. Tsuji K. Doi T. Ohno S. Takenaka K. Kobori A. Ninomiya T. Yoshida H. Takano M. et al.High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.J. Am. Coll. Cardiol. 2005; 46: 2100-2106Crossref PubMed Scopus (99) Google Scholar, 29Pfahnl A.E. Viswanathan P.C. Weiss R. Shang L.L. Sanyal S. Shusterman V. Kornblit C. London B. Dudley Jr., S.C. A sodium channel pore mutation causing Brugada syndrome.Heart Rhythm. 2007; 4: 46-53Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 30Valdivia C.R. Ackerman M.J. Tester D.J. Wada T. McCormack J. Ye B. Makielski J.C. A novel SCN5A arrhythmia mutation, M1766L, with expression defect rescued by mexiletine.Cardiovasc. Res. 2002; 55: 279-289Crossref PubMed Scopus (77) Google Scholar, 31Valdivia C.R. Tester D.J. Rok B.A. Porter C.B. Munger T.M. Jahangir A. Makielski J.C. Ackerman M.J. A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs.Cardiovasc. Res. 2004; 62: 53-62Crossref PubMed Scopus (106) Google Scholar For these experiments, cells stably expressing loss-of-function variants were generated as described above. The cells were incubated for 24 h at 30°C, or at 37°C with or without 500 μM mexiletine hydrochloride (Sigma), washed with HEK media, and were patch clamped as described above.
AssayGeneralClass: BAO:0000062 patch clamp
AssayMaterialUsed: CLO:0037237 HEK293-derived cell
AssayDescription: HEK293T-derived cells stably expressing wild type or variant SCN5A were patch clamped and currents elicited in response to activation, inactivation, and recovery from inactivation were recorded, as well as late current measurements.
AssayReadOutDescription: Peak current density relative to wild type, which was set to 100%
AssayRange: %
AssayNormalRange: Peak current density 75-125% of wild type
AssayAbnormalRange: Peak current density 10-50% of wildtype
AssayIndeterminateRange: Peak current density 50-75% of wildtype
ValidationControlPathogenic: 0
ValidationControlBenign: 10
Replication: At least 2 independent transfections and at least 10 replicate cells per variant (see ReplicateCount in FunctionalAssayResult annotations for each variant).
StatisticalAnalysisDescription: Two-tailed t tests or two-tailed Mann-Whitney U tests were used to compare variant parameters between groups of variants, while differences in dispersion between groups were tested with Levene’s test.
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 100
AssayResultAssertion: Normal
ReplicateCount: 471
StandardErrorMean: 3.7
ControlType: Normal; wild type
Comment: This variant (wildtype) had normal function. All other variant parameters were normalized to the values of wildtype. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 59.3
AssayResultAssertion: Indeterminate
ReplicateCount: 30
StandardErrorMean: 8.3
Comment: This variant had mild loss of function (peak current >50% and <75% of wildtype), therefore it was considered inconclusive and neither abnormal nor normal in vitro function. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 28.4
AssayResultAssertion: Abnormal
ReplicateCount: 13
StandardErrorMean: 8.6
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 45.3
AssayResultAssertion: Abnormal
ReplicateCount: 31
StandardErrorMean: 5.1
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1).
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 37.2
AssayResultAssertion: Abnormal
ReplicateCount: 26
StandardErrorMean: 3.8
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 23.1
AssayResultAssertion: Abnormal
ReplicateCount: 33
StandardErrorMean: 3.2
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 89.5
AssayResultAssertion: Normal
ReplicateCount: 29
StandardErrorMean: 14.6
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.9
AssayResultAssertion: Abnormal
ReplicateCount: 18
StandardErrorMean: 0.5
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 5.4
AssayResultAssertion: Abnormal
ReplicateCount: 19
StandardErrorMean: 1.5
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 14.8
AssayResultAssertion: Abnormal
ReplicateCount: 27
StandardErrorMean: 2.5
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 78.9
AssayResultAssertion: Normal
ReplicateCount: 38
StandardErrorMean: 7.2
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 43.3
AssayResultAssertion: Abnormal
ReplicateCount: 14
StandardErrorMean: 12.2
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 59.7
AssayResultAssertion: Indeterminate
ReplicateCount: 41
StandardErrorMean: 6.3
Comment: This variant had mild loss of function (peak current >50% and <75% of wildtype), therefore it was considered inconclusive and neither abnormal nor normal in vitro function. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 10.2
AssayResultAssertion: Abnormal
ReplicateCount: 12
StandardErrorMean: 3.4
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.3
AssayResultAssertion: Abnormal
ReplicateCount: 24
StandardErrorMean: 0.3
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0
AssayResultAssertion: Abnormal
ReplicateCount: 11
StandardErrorMean: 0
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 3
AssayResultAssertion: Abnormal
ReplicateCount: 16
StandardErrorMean: 1.5
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 32.6
AssayResultAssertion: Abnormal
ReplicateCount: 10
StandardErrorMean: 6.2
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 36
AssayResultAssertion: Abnormal
ReplicateCount: 14
StandardErrorMean: 6
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 13.9
AssayResultAssertion: Abnormal
ReplicateCount: 15
StandardErrorMean: 2.8
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 3.5
AssayResultAssertion: Abnormal
ReplicateCount: 29
StandardErrorMean: 0.8
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.2
AssayResultAssertion: Abnormal
ReplicateCount: 25
StandardErrorMean: 0.2
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 102.6
AssayResultAssertion: Normal
ReplicateCount: 31
StandardErrorMean: 16.5
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 1.6
AssayResultAssertion: Abnormal
ReplicateCount: 15
StandardErrorMean: 0.7
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 12
AssayResultAssertion: Abnormal
ReplicateCount: 10
StandardErrorMean: 2.2
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 102.4
AssayResultAssertion: Normal
ReplicateCount: 39
StandardErrorMean: 15.5
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 47
AssayResultAssertion: Indeterminate
ReplicateCount: 10
StandardErrorMean: 15.5
Comment: This variant had a mix of multiple abnormalities: a partial loss of function of peak current (10-50% of wildtype) and a gain of function >10mV shift in activation voltage. Therefore it was considered to have inconclusive in vitro properties (neither normal nor abnormal in vitro function). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 114.7
AssayResultAssertion: Normal
ReplicateCount: 42
StandardErrorMean: 15.2
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 36
AssayResultAssertion: Abnormal
ReplicateCount: 19
StandardErrorMean: 5.9
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 121.4
AssayResultAssertion: Normal
ReplicateCount: 34
StandardErrorMean: 13.2
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 1.1
AssayResultAssertion: Abnormal
ReplicateCount: 27
StandardErrorMean: 0.8
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 29.8
AssayResultAssertion: Abnormal
ReplicateCount: 13
StandardErrorMean: 5.7
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 3.2
AssayResultAssertion: Abnormal
ReplicateCount: 16
StandardErrorMean: 0.5
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.8
AssayResultAssertion: Abnormal
ReplicateCount: 23
StandardErrorMean: 0.6
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0
AssayResultAssertion: Abnormal
ReplicateCount: 43
StandardErrorMean: 0
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 16
AssayResultAssertion: Abnormal
ReplicateCount: 26
StandardErrorMean: 2.3
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 2.9
AssayResultAssertion: Abnormal
ReplicateCount: 20
StandardErrorMean: 2.1
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 117.2
AssayResultAssertion: Abnormal
ReplicateCount: 36
StandardErrorMean: 11.7
Comment: This variant had normal peak current and increased late current (>1% of peak), therefore it was considered a GOF variant (in vitro features consistent with Long QT Syndrome Type 3). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 21
AssayResultAssertion: Abnormal
ReplicateCount: 12
StandardErrorMean: 5.1
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 38.9
AssayResultAssertion: Abnormal
ReplicateCount: 27
StandardErrorMean: 7.2
Comment: This variant had partial loss of function of peak current (10-50% of wildtype) and a >10mV loss of function shift in Vhalf activation, therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 120.5
AssayResultAssertion: Normal
ReplicateCount: 41
StandardErrorMean: 10.5
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 105.3
AssayResultAssertion: Normal
ReplicateCount: 41
StandardErrorMean: 10.8
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 77.5
AssayResultAssertion: Normal
ReplicateCount: 30
StandardErrorMean: 8.6
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 41.7
AssayResultAssertion: Abnormal
ReplicateCount: 15
StandardErrorMean: 10.8
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 63.8
AssayResultAssertion: Indeterminate
ReplicateCount: 25
StandardErrorMean: 10.1
Comment: This variant had mild loss of function (peak current >50% and <75% of wildtype), therefore it was considered inconclusive and neither abnormal nor normal in vitro function. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.9
AssayResultAssertion: Abnormal
ReplicateCount: 12
StandardErrorMean: 0.6
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 68.1
AssayResultAssertion: Indeterminate
ReplicateCount: 18
StandardErrorMean: 8.7
Comment: This variant had mild loss of function (peak current >50% and <75% of wildtype), therefore it was considered inconclusive and neither abnormal nor normal in vitro function. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 32
AssayResultAssertion: Abnormal
ReplicateCount: 31
StandardErrorMean: 5
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 1.2
AssayResultAssertion: Abnormal
ReplicateCount: 11
StandardErrorMean: 0.7
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 3.4
AssayResultAssertion: Abnormal
ReplicateCount: 22
StandardErrorMean: 0.8
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0
AssayResultAssertion: Abnormal
ReplicateCount: 39
StandardErrorMean: 0
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.6
AssayResultAssertion: Abnormal
ReplicateCount: 25
StandardErrorMean: 0.4
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 28.5
AssayResultAssertion: Abnormal
ReplicateCount: 21
StandardErrorMean: 7.6
Comment: This variant had partial loss of function of peak current (10-50% of wildtype) and a >10mV loss of function shift in Vhalf activation, therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 113.2
AssayResultAssertion: Normal
ReplicateCount: 30
StandardErrorMean: 13.9
Comment: This variant had normal function (75-125% of wildtype peak current, <1% late current, no large perturbations to other parameters). These in vitro features are consistent with non-disease causing variants. (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0
AssayResultAssertion: Abnormal
ReplicateCount: 24
StandardErrorMean: 0
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 1.3
AssayResultAssertion: Abnormal
ReplicateCount: 67
StandardErrorMean: 0.3
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 0.8
AssayResultAssertion: Abnormal
ReplicateCount: 14
StandardErrorMean: 0.6
Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
-
Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
AssayResult: 34.2
AssayResultAssertion: Abnormal
ReplicateCount: 14
StandardErrorMean: 6.7
Comment: This variant had partial loss of function of peak current (10-50% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
Tags
- ClinVarID:67633
- CAID:CA014455
- ClinVarID:67747
- ClinVarID:229230
- AssayRangeType:Quantitative
- CAID:CA016182
- MONDO:0011001
- ClinVarID:67857
- Variant:1
- ClinVarID:67640
- Variant:26
- CAID:CA060381
- ClinVarID:67642
- Variant:50
- CAID:CA018042
- CAID:CA352145324
- CAID:CA015938
- Variant:55
- Variant:47
- CAID:CA016228
- ClinVarID:48294
- FuncAssay:1
- ClinVarID:68047
- ClinVarID:67752
- Variant:57
- ClinVarID:67869
- CAID:CA016384
- CAID:CA018516
- CAID:CA352146767
- Variant:6
- CAID:CA064645
- Variant:15
- Variant:30
- ClinVarID:67830
- CGType:FunctionalAssayResult
- Variant:80
- CAID:CA019833
- CAID:CA017557
- ClinVarID:67876
- CAID:CA019844
- Variant:79
- CAID:CA015925
- CAID:CA018863
- CAID:CA016059
- ClinVarID:67721
- CAID:CA017946
- CAID:CA016428
- ClinVarID:67864
- CAID:CA018048
- Variant:56
- CAID:CA352139743
- Variant:77
- Variant:76
- Variant:28
- Variant:46
- ClinVarID:67952
- ClinVarID:67920
- AssayControl:Normal
- Variant:54
- ClinVarID:9399
- CAID:CA017513
- Variant:35
- Variant:20
- Variant:17
- CAID:CA352149766
- Variant:12
- Variant:18
- Variant:45
- ClinVarID:67940
- Variant:3
- Variant:32
- Variant:9
- CAID:CA018747
- ClinVarID:67874
- ClinVarID:67820
- CAID:CA018812
- Variant:19
- Variant:43
- Variant:8
- CAID:CA057036
- CAID:CA016076
- CAID:CA352149916
- Variant:61
- Variant:69
- ClinVarID:67960
- ClinVarID:67727
- Variant:60
- Variant:41
- ClinVarID:67873
- CAID:CA014305
- Variant:25
- Variant:13
- CAID:CA017913
- Variant:51
- Variant:59
- ClinVarID:628262
- Variant:7
- ClinVarID:67866
- CAID:CA019709
- CAID:CA017955
- ClinVarID:67884
- CAID:CA352143498
- CAID:CA352143353
- CAID:CA018943
- Variant:52
- ClinVarID:67951
- ClinVarID:67732
- CAID:CA016482
- Variant:71
- ClinVarID:201546
- CAID:CA016490
- ClinVarID:67737
- ClinVarID:67719
- Variant:68
- CAID:CA018163
- ClinVarID:67867
- CAID:CA017796
- CG:BulkAnnotation
- CAID:CA352144555
- ClinVarID:201523
- CAID:CA018503
- ClinVarID:67854
- Variant:14
- ClinVarID:68045
- Variant:64
- ClinVarID:67810
- ClinVarID:67756
- Variant:62
- CAID:CA014429
- Variant:81
- Variant:27
- CAID:CA017969
- BAO:0000062
- ClinVarID:67918
- Variant:22
- ClinVarID:67742
- Variant:39
- ClinVarID:67720
- Variant:67
- Variant:21
- Variant:66
- Variant:33
- CAID:CA016274
- CAID:CA018848
- Variant:38
- ClinVarID:68031
- CAID:CA017808
- CAID:CA352142022
- ValidationControl:WildType
- CAID:CA352141945
- Variant:53
- ClinVarID:67634
- CAID:CA017399
- ClinVarID:518750
- CAID:CA015974
- CAID:CA017837
- CAID:CA018904
- Variant:5
- Variant:70
- CGType:FunctionalAssay
- CLO:0037237
- ClinVarID:67757
- ClinVarID:67957
- ClinVarID:67635
- CAID:CA014324
- Variant:2
- CAID:CA017472
- CAID:CA018079
- CAID:CA019516
- ClinVarID:67852
- CAID:CA014336
- UO:0000187
Annotators
URL
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