- Mar 2021
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: 1.5
AssayResultAssertion: Abnormal
Approximation: Exact assay result value not reported; value estimated from Figure 3e.
-
WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: <1
AssayResultAssertion: Abnormal
Approximation: Exact assay result value not reported; value estimated from Figure 3e.
-
WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: 1
AssayResultAssertion: Abnormal
Approximation: Exact assay result value not reported; value estimated from Figure 3e.
-
WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: 3
AssayResultAssertion: Abnormal
Approximation: Exact assay result value not reported; value estimated from Figure 3e.
-
WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: 1
AssayResultAssertion: Abnormal
ControlType: Abnormal; empty vector
Approximation: Exact assay result value not reported; value estimated from Figure 3e.
-
WT-PALB2 was associated with robust formation of damage-induced RAD51 foci, whereas the four variants were associated with defective foci formation (Fig. 3d, e).
AssayResult: 27
AssayResultAssertion: Normal
StandardDeviation: 14
ControlType: Normal; wild type PALB2 cDNA
Approximation: Exact assay result and standard deviation values not reported; values estimated from Figure 3e.
-
ImmunofluorescenceLive cell imaging and microirradiation studies of HeLa cells transfected with peYFP-C1-PALB2 WT or variant constructs were carried out with a Leica TCS SP5 II confocal microscope. To monitor the recruitment of YFP-PALB2 to laser-induced DNA damage sites, cells were microirradiated in the nucleus for 200 ms using a 405-nm ultraviolet (UV) laser and imaged every 30 seconds for 15 minutes. Fluorescence intensity of YFP-PALB2 at DNA damage sites relative to an unirradiated nuclear area was quantified (Supplemental Materials). Cyclin A–positive HeLa cells treated with siCtrl and siRNA against PALB2 were complemented with wild-type and mutant FLAG-tagged PALB2 expression constructs, exposed to 2 Gy of γ-IR, incubated for 6 hours, and subjected to immunofluorescence for RAD51 foci. HeLa cells were fixed with 4% (w/v) paraformaldehyde for 10 minutes at room temperature, washed with tris-buffered saline (TBS), and fixed again with ice-cold methanol for 5 minutes at −20 °C. Cells were incubated for 1 hour at room temperature with the anti-RAD51 (1:7000, B-bridge International, 70-001) and anticyclin A (1:400, BD Biosciences, 611268), and incubated for 1 hour at room temperature with the Alexa Fluor 568 goat antirabbit (Invitrogen, A-11011) and Alexa Fluor 647 goat antimouse (Invitrogen, A-21235) secondary antibodies. Z-stack images were acquired on a Leica CTR 6000 microscope and the number of RAD51 foci per cyclin A–positive cells expressing the indicated YFP-PALB2 constructs was scored with Volocity software v6.0.1 (Perkin–Elmer Improvision). Results represent the mean (± SD) of three independent trials (n = 50 cells per condition). HEK293T cells transfected with PALB2 expression constructs were also subjected to immunofluorescence for PALB2 using the monoclonal anti-FLAG M2 antibody (Sigma) and the Alexa Fluor 568 goat antimouse (Life Technologies) secondary antibody.
AssayGeneralClass: BAO:0000450 fluorescence microscopy
AssayMaterialUsed: CLO:0003684 HeLa cell
AssayDescription: HeLa cells were treated with PALB2 siRNA and transfected with peYFP-PALB2 expressing PALB2 variants (or empty vector), followed by exposure to 2 Gy of γ-IR. Six hours after irradiation, cells were subjected to immunofluorescence for RAD51 foci (where foci formation serves as marker of normal DNA damage repair function).
AssayReadOutDescription: The number of RAD51 foci per cyclin A-positive cells expressing the indicated YFP-PALB2 constructs.
AssayRange: foci/cell
AssayNormalRange: Not reported
AssayAbnormalRange: Not reported
AssayIndeterminateRange: Not reported
ValidationControlPathogenic: 0
ValidationControlBenign: 0
Replication: Three independent experiments with 50 cells per condition
StatisticalAnalysisDescription: Kruskal–Wallis test with Dunn's multiple comparison post-test
-
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: 5.3
AssayResultAssertion: Normal
StandardErrorMean: 0.46
Tags
- AssayControl:Abnormal
- ClinVarID:126582
- AssayControl:Normal
- CGType:FunctionalAssayResult
- Variant:2
- CGType:FunctionalAssay
- CAID:CA339433
- ClinVarID:657328
- ClinVarID:230588
- CAID:CA151212
- CAID:CA197176
- Variant:42
- ValidationControl:WildType
- CLO:0003684
- Variant:85
- BAO:0000450
- FuncAssay:1
- ClinVarID:187262
- MONDO:0016419
- CG:BulkAnnotation
- ValidationControl:Benign
- CAID:CA279502031
- CAID:CA10580054
- ClinVarID:216752
- FuncAssay:2
- Variant:56
- Variant:4
- HGNC:26144
- AssayRangeType:Quantitative
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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RAD51 foci assayHeLa cells were seeded on glass coverslips in 6-well plates at 225 000 cells per well. Knockdown of PALB2 was performed 18 h later with 50 nM PALB2 siRNA using Lipofectamine RNAiMAX (Invitrogen). After 5 h, cells were subjected to double thymidine block. Briefly, cells were treated with 2 mM thymidine for 18 h and release into fresh media for 9 h. Complementation using 800 ng of the peYFP-C1 empty vector or the indicated siRNA-resistant YFP-PALB2 construct was carried out with Lipofectamine 2000 during that release time. Then, cells were treated with 2 mM thymidine for 17 h and protected from light from this point on. After 2 h of release from the second block, cells were irradiated with 2 Gy and processed for immunofluorescence 4 h post-irradiation. Unless otherwise stated, all immunofluorescence dilutions were prepared in PBS and incubations performed at room temperature with intervening washes in PBS. Cell fixation was carried out by incubation with 4% paraformaldehyde for 10 min followed by 100% ice-cold methanol for 5 min at −20°C. This was succeeded by permeabilization in 0.2% Triton X-100 for 5 min and a quenching step using 0.1% sodium borohydride for 5 min. After blocking for 1 h in a solution containing 10% goat serum and 1% BSA, cells were incubated for 1 h with primary antibodies anti-RAD51 (1 :7000, B-bridge International, #70–001) and anti-cyclin A (1:400, BD Biosciences, #611268) diluted in 1% BSA. Secondary antibodies Alexa Fluor 568 goat anti-rabbit (Invitrogen, #A-11011) and Alexa Fluor 647 goat anti-mouse (Invitrogen, #A-21235) were diluted 1:1000 in 1% BSA and applied for 1 h. Nuclei were stained for 10 min with 1 μg/ml 4,6-diamidino-2-phenylindole (DAPI) prior to mounting onto slides with 90% glycerol containing 1 mg/ml paraphenylenediamine anti-fade reagent. Z-stack images were acquired on a Leica CTR 6000 microscope using a 63× oil immersion objective, then deconvolved and analyzed for RAD51 foci formation with Volocity software v6.0.1 (Perkin-Elmer Improvision). The number of RAD51 foci per cyclin A-positive cells expressing the indicated YFP-PALB2 constructs was scored using automatic spot counting by Volocity software and validated manually. Data from three independent trials (total n = 225 cells per condition) were analyzed for outliers using the ROUT method (Q = 1.0%) in GraphPad Prism v6.0 and the remaining were reported in a scatter dot plot. Intensity values, also provided by Volocity, of 500 RAD51 foci from a representative trial were normalized to the WT mean and reported in a scatter dot plot. Horizontal lines on the plots designate the mean values.
AssayGeneralClass: BAO:0000450 fluorescence microscopy
AssayMaterialUsed: CLO:0003684 HeLa cell
AssayDescription: HeLa cells were treated with PALB2 siRNA and synchronized to G1/S phase by double thymidine block. Cells were then transfected with peYFP-PALB2 expressing PALB2 variants (or empty vector) and irradiated with 2 Gy. Four hours after irradiation, cells were subjected to immunofluorescence for RAD51 foci (where foci formation serves as marker of normal DNA damage repair function).
AssayReadOutDescription: The number of RAD51 foci per cyclin A-positive cells expressing the indicated YFP-PALB2 constructs was scored and presented as percentage change relative to the wild type mean RAD51 foci number per cell.
AssayRange: %
AssayNormalRange: Not reported
AssayAbnormalRange: Not reported
AssayIndeterminateRange: Not reported
ValidationControlPathogenic: 1
ValidationControlBenign: 3
Replication: Three independent experiments, each with 225 cells per condition
StatisticalAnalysisDescription: Kruskal–Wallis test with Dunn's multiple comparison post-test
-
SUPPLEMENTARY DATA
AssayResult: 38
AssayResultAssertion: Abnormal
PValue: < 0.0001
Approximation: Exact assay result value not reported; value estimated from Figure 6C.
-
SUPPLEMENTARY DATA
AssayResult: -96
AssayResultAssertion: Abnormal
PValue: < 0.0001
ControlType: Abnormal; empty vector
-
SUPPLEMENTARY DATA
AssayResult: 0
AssayResultAssertion: Normal
ControlType: Normal; wild type PALB2 cDNA
-
SUPPLEMENTARY DATA
AssayResult: -34
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: -11
AssayResultAssertion: Indeterminate
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -4
AssayResultAssertion: Indeterminate
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -14
AssayResultAssertion: Indeterminate
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -56
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: -6
AssayResultAssertion: Normal
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -25
AssayResultAssertion: Abnormal
PValue: < 0.01
-
SUPPLEMENTARY DATA
AssayResult: -31
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: -16
AssayResultAssertion: Normal
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -10
AssayResultAssertion: Normal
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -21
AssayResultAssertion: Indeterminate
PValue: < 0.01
-
SUPPLEMENTARY DATA
AssayResult: -20
AssayResultAssertion: Indeterminate
PValue: < 0.05
-
SUPPLEMENTARY DATA
AssayResult: 8
AssayResultAssertion: Indeterminate
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -29
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: -98
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: -36
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: 3
AssayResultAssertion: Indeterminate
PValue: Not reported
-
SUPPLEMENTARY DATA
AssayResult: -32
AssayResultAssertion: Abnormal
PValue: < 0.0001
-
SUPPLEMENTARY DATA
AssayResult: 85.76
AssayResultAssertion: Indeterminate
PValue: 0.0445
Comment: Exact values reported in Table S3.
Tags
- AssayControl:Abnormal
- ClinVarID:126738
- CAID:CA186642
- Variant:22
- AssayControl:Normal
- Variant:14
- CAID:CA7963465
- Variant:45
- CAID:CA10579934
- CAID:CA151233
- CLO:0003684
- ValidationControl:WildType
- BAO:0000450
- ClinVarID:126755
- ClinVarID:126774
- MONDO:0016419
- ClinVarID:126652
- ClinVarID:126699
- UO:0000187
- FuncAssay:3
- ValidationControl:Benign
- ClinVarID:241553
- ClinVarID:126758
- CAID:CA299799
- CAID:CA269654
- ClinVarID:126716
- ClinVarID:126590
- Variant:15
- FuncAssay:2
- ValidationControl:Pathogenic
- CAID:CA288386
- Variant:18
- Variant:11
- Variant:10
- AssayRangeType:Quantitative
- Variant:4
- Variant:32
- CAID:CA331796
- Variant:27
- CAID:CA299750
- ClinVarID:126669
- Variant:2
- CGType:FunctionalAssayResult
- CGType:FunctionalAssay
- ClinVarID:126782
- ClinVarID:657666
- ClinVarID:657328
- CAID:CA151236
- Variant:37
- CAID:CA395139336
- ClinVarID:232977
- Variant:1
- Variant:8
- ClinVarID:182774
- Variant:31
- Variant:38
- FuncAssay:1
- CAID:CA151242
- CG:BulkAnnotation
- CAID:CA279502031
- Variant:41
- CAID:CA269666
- CAID:CA168501
- CAID:CA395144524
- ClinVarID:126682
- CAID:CA269636
- ClinVarID:183828
- Variant:24
- CAID:CA161315
- HGNC:26144
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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sensitivity to PARPi treatment using a cellular proliferation assay
AssayGeneralClass: BAO:0002805 cell proliferation assay
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; exposure to PARP inhibitor Olaparib for 48 h inhibits end-joining mediated by PARP and sensitizes cells to DNA damage; cell survival is measured by FACS 24 h after Olaparib washout
AssayReadOutDescription: Relative resistance to PARPi represented as cell survival relative to wild type, which was set to 100%
AssayRange: %
AssayNormalRange: PARPi resistance levels comparable to that of cells expressing wild type PALB2; no numeric threshold given
AssayAbnormalRange: PARPi resistance levels ≤30% of wild type
AssayIndeterminateRange: Not reported
ValidationControlPathogenic: 12
ValidationControlBenign: 9
Replication: 2 independent experiments
StatisticalAnalysisDescription: Not reported
-
Source Data
AssayResult: 26.03
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 11.42
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 24.27
AssayResultAssertion: Abnormal
ReplicateCount: Not reported
StandardErrorMean: Not reported
Comment: Exact values reported in “Supplementary Data 1” file; result for this variant not reported in “Source Data” file.
-
Source Data
AssayResult: 96.22
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 16.7
Comment: Exact values reported in “Source Data” file. Discrepancy in “Supplementary Data 1” file: nucleotide reported as c.3191A>G.
-
Source Data
AssayResult: 15.23
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 6.42
Comment: Exact values reported in “Source Data” file. Discrepancy in “Source Data” file: protein reported as Q899X.
-
Source Data
AssayResult: 52.23
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 6.33
Comment: Exact values reported in “Source Data” file. Discrepancy in “Source Data” file: protein reported as I1037R.
-
Source Data
AssayResult: 74.36
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 1.89
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 87.27
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 1.3
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 17.29
AssayResultAssertion: Abnormal
ReplicateCount: 3
StandardErrorMean: 6.81
ControlType: Abnormal; empty vector (set 5)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.86
AssayResultAssertion: Abnormal
ReplicateCount: 3
StandardErrorMean: 2.39
ControlType: Abnormal; empty vector (set 4)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 34.03
AssayResultAssertion: Abnormal
ReplicateCount: 3
StandardErrorMean: 10.86
ControlType: Abnormal; empty vector (set 3)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 12.78
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 3.65
ControlType: Abnormal; empty vector (set 2)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.93
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 0.78
ControlType: Abnormal; empty vector (set 1)
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 100
AssayResultAssertion: Normal
ReplicateCount: 38
StandardErrorMean: 0
ControlType: Normal; wild type
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 102.22
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 8.29
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 21.7
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.42
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 55.4
AssayResultAssertion: Not reported
ReplicateCount: 4
StandardErrorMean: 13.29
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 17.5
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 7.75
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 102.7
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardErrorMean: 12.82
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 94.47
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 0.99
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 13.87
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.32
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 93.44
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 2.24
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 9.67
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.31
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 109.07
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 9.27
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 98.64
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 5.5
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 102.88
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 20.71
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 16.6
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 4.35
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 103.21
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 8.98
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 108.27
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 16.12
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 98.43
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 14.96
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 102.57
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardErrorMean: 11.51
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 103.83
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 3.67
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 87.51
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 4.4
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 56.67
AssayResultAssertion: Not reported
ReplicateCount: 4
StandardErrorMean: 12.4
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 85.13
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 15.04
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 108.56
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 19.59
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.42
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 0.01
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 99.69
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 3.09
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 12.35
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.48
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 14.79
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 7.81
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 84.41
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 1.42
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 25.09
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 3.48
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 97.37
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 5.14
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 12.77
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 5.34
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 78.91
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 6.86
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 8.41
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.95
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 24.31
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 5.23
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 14.78
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 9.34
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 81.17
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 9.32
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 91.11
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardErrorMean: 17.74
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 26.39
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.11
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 94.54
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 19.94
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 86.26
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 4.22
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 7.73
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 2.25
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 29.04
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 7.24
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 115.45
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 11.81
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 78.3
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 11.75
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 86.54
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 11.96
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 87.96
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 10.31
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 78.2
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 7.31
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 103.53
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 7.06
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 19.46
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 1.75
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 64.92
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 8.7
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 11.06
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 2.4
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 117.58
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 0.81
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 10.68
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 0.32
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 23.96
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 7.6
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 120.54
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 11.09
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 74.18
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 6.49
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 95.74
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 14.87
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 83.96
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 9.89
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 94.84
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 20.56
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 17.43
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 5.19
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 108.51
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 17.71
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 67.82
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 10.97
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 72.7
AssayResultAssertion: Not reported
ReplicateCount: 3
StandardErrorMean: 9.73
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 9.68
AssayResultAssertion: Abnormal
ReplicateCount: 2
StandardErrorMean: 3.44
Comment: Exact values reported in “Source Data” file.
-
Source Data
AssayResult: 115.71
AssayResultAssertion: Not reported
ReplicateCount: 2
StandardErrorMean: 3.09
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.
Tags
- ClinVarID:126738
- Variant:22
- AssayControl:Normal
- Variant:26
- CAID:CA16620118
- CAID:CA151233
- CAID:CA395141224
- CLO:0037317
- ClinVarID:126613
- ClinVarID:126699
- ClinVarID:241553
- CAID:CA395144928
- CAID:CA210470
- CAID:CA395139673
- ClinVarID:126590
- Variant:18
- ClinVarID:420826
- Variant:10
- Variant:68
- ClinVarID:182786
- ClinVarID:126669
- Variant:2
- CGType:FunctionalAssay
- Variant:51
- ClinVarID:219647
- BAO:0002805
- Variant:53
- CAID:CA196017
- Variant:29
- Variant:33
- Variant:37
- CAID:CA197176
- Variant:34
- Variant:61
- CAID:CA299747
- CAID:CA279524947
- CAID:CA395137656
- Variant:59
- CAID:CA279502031
- Variant:13
- Variant:41
- Variant:55
- Variant:63
- ClinVarID:126747
- ClinVarID:128136
- CAID:CA185966
- ClinVarID:182741
- CAID:CA167348
- Variant:62
- Variant:46
- Variant:14
- Variant:6
- ClinVarID:126582
- CAID:CA288398
- CAID:CA10579985
- CAID:CA395141474
- CAID:CA395139401
- ClinVarID:546043
- Variant:9
- Variant:54
- CAID:CA163622
- ValidationControl:WildType
- CAID:CA279530867
- Variant:70
- ClinVarID:126761
- MONDO:0016419
- Variant:17
- CAID:CA288478
- CAID:CA161327
- CAID:CA251717
- CAID:CA269551
- CAID:CA294562
- Variant:11
- CAID:CA288386
- AssayRangeType:Quantitative
- CAID:CA299663
- Variant:32
- ClinVarID:484164
- ClinVarID:530038
- Variant:36
- ClinVarID:1245
- Variant:44
- Variant:67
- ClinVarID:657328
- ClinVarID:182790
- ClinVarID:922719
- ClinVarID:126711
- ClinVarID:484186
- ClinVarID:186939
- ClinVarID:126740
- ClinVarID:126609
- CAID:CA395141313
- CAID:CA395145110
- CAID:CA250432
- Variant:43
- ClinVarID:126670
- ClinVarID:126600
- ClinVarID:461007
- ClinVarID:126607
- Variant:56
- ClinVarID:216752
- Variant:24
- Variant:25
- HGNC:26144
- ClinVarID:186824
- CAID:CA161333
- Variant:45
- Variant:23
- CAID:CA10579934
- Variant:52
- Variant:48
- ClinVarID:142468
- CAID:CA494163316
- ClinVarID:126774
- CAID:CA269492
- CAID:CA658658444
- CAID:CA395144208
- Variant:30
- CAID:CA395125757
- ClinVarID:126683
- CAID:CA16621924
- ValidationControl:Benign
- CAID:CA192169
- ClinVarID:460996
- CAID:CA7963653
- CAID:CA269654
- ClinVarID:1246
- CAID:CA299784
- ClinVarID:186840
- CAID:CA294407
- CAID:CA151229
- Variant:4
- Variant:64
- CAID:CA331796
- CAID:CA350039
- CAID:CA395121845
- Variant:50
- CAID:CA395137855
- ClinVarID:126706
- Variant:12
- CAID:CA151250
- CAID:CA151230
- CAID:CA395142764
- ClinVarID:484219
- ClinVarID:232977
- Variant:69
- Variant:8
- Variant:38
- Variant:58
- Variant:60
- CAID:CA251004
- Variant:57
- Variant:65
- ClinVarID:185518
- ClinVarID:126594
- ClinVarID:187262
- CAID:CA151242
- CAID:CA151222
- Variant:7
- ClinVarID:1243
- ClinVarID:126623
- CAID:CA161315
- AssayControl:Abnormal
- Variant:21
- CAID:CA7963465
- ClinVarID:142079
- ClinVarID:230588
- CAID:CA151212
- Variant:28
- Variant:42
- Variant:40
- Variant:19
- ClinVarID:229718
- ClinVarID:182773
- CAID:CA164468
- Variant:35
- Variant:66
- Variant:20
- Variant:3
- UO:0000187
- FuncAssay:3
- CAID:CA161342
- ClinVarID:126758
- ClinVarID:134994
- Variant:5
- ValidationControl:Pathogenic
- Variant:15
- FuncAssay:2
- ClinVarID:126630
- Variant:49
- Variant:39
- Variant:27
- CGType:FunctionalAssayResult
- Variant:16
- CAID:CA339433
- ClinVarID:567901
- CAID:CA163908
- CAID:CA395144862
- CAID:CA196291
- Variant:1
- CAID:CA195974
- Variant:31
- FuncAssay:1
- ClinVarID:126749
- CG:BulkAnnotation
- CAID:CA395122261
- CAID:CA923726356
- CAID:CA269625
- CAID:CA395137985
- CAID:CA10580054
- ClinVarID:126595
- CAID:CA151239
- Variant:47
Annotators
URL
-
-
www.cell.com www.cell.com
-
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)
-
-
jmg.bmj.com jmg.bmj.com
-
This new quantitative assay, based on both RT-QMPSF and RT-MLPA, was first validated on 31 lymphoblastoid cell lines derived from patients with LFS harbouring different germline heterozygous TP53 variants
AssayGeneralClass: BAO:0010044 targeted transcriptional assay
AssayMaterialUsed: BTO:0000773 lymphoblastoid cell line derived from control individuals or individuals with germline TP53 variants
AssayDescription: Comparative transcriptomic analysis using RNA-Seq to compare EBV cell lines of wild type and pathogenic TP53 in the context of genotoxic stress induced by doxorubicin treatment. p53 RNA levels were evaluated and expressed as a percentage of the mean levels obtained for the three wild-type TP53 individuals.
AdditionalDocument: PMID: 23172776
AssayReadOutDescription: The p53 mRNA levels were expressed as a ratio of the normal values obtained for 3 TP53 wild-type control individuals.
AssayRange: UO:0000187 the p53 RNA levels were evaluated and expressed as a percentage of the mean levels obtained for three wild-type TP53 individuals.
AssayNormalRange: N/A
AssayAbnormalRange: N/A
AssayIndeterminateRange: N/A
AssayNormalControl: wild type TP53
AssayAbnormalControl: LFS patient cells
ValidationControlPathogenic: 8 Individuals with dominant-negative TP53 missense variants, 10 Individuals with null TP53 variants, and 13 Individuals with other TP53 missense variants
ValidationControlBenign: 3 patients with wild type TP53
Replication: experiments were performed in triplicates.
StatisticalAnalysisDescription: Differentially expressed genes between doxorubicin-treated and untreated cells were arbitrarily defined using, as filters, a P<0.01 and fold-change cutoffs >2 or <2, for up and down regulation, respectively. The resultant signal information was analyzed using one-way analysis of variance (ANOVA, P= 0.001), assuming normality but not equal variances with a Benjamani–Hochberg correction for multiple comparisons using three groups: controls, null, and missense mutations.
SignificanceThreshold: P=0.001
Comment: statistical analysis and P value from previous publication.
-
- Feb 2021
-
jmg.bmj.com jmg.bmj.com
-
Supplemental material
AssayResult: 82
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 80
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 69
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 99
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 98
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 77
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 105
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 96
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 104
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 99
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 83
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 91
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 86
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 56
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 61
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 51
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 66
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 60
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 65
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 66
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 45
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 58
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 49
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 83
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 84
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 91
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 94
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 97
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 98
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 96
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 105
AssayResultAssertion: Normal
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 88
AssayResultAssertion: Normal
ControlType: Normal, wild type TP53 from control 3
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 95
AssayResultAssertion: Normal
ControlType: Normal, wild type TP53 from control 2
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 100
AssayResultAssertion: Normal
ControlType: Normal, wild type TP53 from control 1
Comment: See Table S2 for details
-
Supplemental material
AssayResult: 7.1
AssayResultAssertion: Abnormal
Comment: See Table S2 for details
Tags
- Variant:22
- ClinVarID:135359
- AssayControl:Normal
- CAID:CA397844631
- CAID:CA1139768487
- Variant:23
- CAID:CA645588668
- Variant:30
- CAID:CA16603034
- CAID:CA16603033
- CAID:CA397836336
- CAID:CA000468
- ClinVarID:458555
- ClinVarID:182957
- CAID:CA000302
- CAID:CA000251
- ClinVarID:420137
- Variant:2
- Variant:50
- Variant:51
- ClinVarID:12347
- Variant:29
- Variant:33
- Variant:37
- ClinVarID:376649
- Variant:24
- Variant:34
- CAID:CA497925664
- ClinVarID:12364
- CAID:CA000308
- Variant:38
- CAID:CA397837761
- CAID:CA645369686
- ClinVarID:12366
- ClinVarID:12374
- CAID:CA000382
- Variant:13
- ClinVarID:127825
- CAID:CA000073
- Variant:46
- Variant:14
- Variant:21
- ClinVarID:376613
- CAID:CA16620623
- ClinVarID:41723
- Variant:9
- ClinVarID:428860
- CAID:CA000434
- CAID:CA16603074
- Variant:28
- ClinVarID:142702
- Variant:40
- ClinVarID:634779
- Variant:19
- ClinVarID:182965
- ClinVarID:127815
- ValidationControl:WildType
- CAID:CA000013
- Variant:3
- CAID:CA497716198
- Variant:5
- ClinVarID:100815
- CAID:CA000493
- ValidationControl:Pathogenic
- ClinVarID:12356
- FuncAssay:2
- CAID:CA397839547
- CAID:CA000374
- Variant:11
- ClinVarID:376659
- Variant:32
- Variant:49
- Variant:27
- Variant:39
- CGType:FunctionalAssayResult
- Variant:44
- CAID:CA000106
- CAID:CA000387
- CAID:CA645588993
- Variant:31
- FuncAssay:1
- CAID:CA000454
- CAID:CA16603066
- ClinVarID:376612
- Variant:43
- Variant:47
- ClinVarID:12379
- CAID:CA000256
Annotators
URL
-