84 Matching Annotations
  1. Dec 2021
  2. Mar 2021
    1. Cells reconstituted with WT-PALB2 showed substantially less sensitivity to olaparib than cells expressing p.A1025R and p.I944N (Fig. 4a). Similar results were observed for cisplatin treatment, although the difference in sensitivity was less pronounced (Fig. 4b). p.L24S, p.L1070P, and p.L35P were also associated with greater sensitivity to olaparib (Fig. 4c) and cisplatin (Fig. 4d) than WT-PALB2.

      AssayResult: 0.01 µM: 70; 0.08 µM: 50; 0.8 µM: 40; 8 µM: 15

      AssayResultAssertion: Abnormal

      Approximation: Exact Olaparib concentrations and assay result values not reported; values estimated from Figures 4a and 4c.

    2. Cells reconstituted with WT-PALB2 showed substantially less sensitivity to olaparib than cells expressing p.A1025R and p.I944N (Fig. 4a). Similar results were observed for cisplatin treatment, although the difference in sensitivity was less pronounced (Fig. 4b). p.L24S, p.L1070P, and p.L35P were also associated with greater sensitivity to olaparib (Fig. 4c) and cisplatin (Fig. 4d) than WT-PALB2.

      AssayResult: 0.01 µM: 50; 0.08 µM: 35; 0.8 µM: 25; 8 µM: 10

      AssayResultAssertion: Abnormal

      Approximation: Exact Olaparib concentrations and assay result values not reported; values estimated from Figures 4a and 4c.

    3. Cells reconstituted with WT-PALB2 showed substantially less sensitivity to olaparib than cells expressing p.A1025R and p.I944N (Fig. 4a). Similar results were observed for cisplatin treatment, although the difference in sensitivity was less pronounced (Fig. 4b). p.L24S, p.L1070P, and p.L35P were also associated with greater sensitivity to olaparib (Fig. 4c) and cisplatin (Fig. 4d) than WT-PALB2.

      AssayResult: 0.01 µM: 60; 0.08 µM: 55; 0.8 µM: 40; 8 µM: 15

      AssayResultAssertion: Abnormal

      Approximation: Exact Olaparib concentrations and assay result values not reported; values estimated from Figures 4a and 4c.

      Comment: This variant was used as an abnormal control in other assays in this publication, but it was not specifically designated as a control in this assay.

    4. Cells reconstituted with WT-PALB2 showed substantially less sensitivity to olaparib than cells expressing p.A1025R and p.I944N (Fig. 4a). Similar results were observed for cisplatin treatment, although the difference in sensitivity was less pronounced (Fig. 4b). p.L24S, p.L1070P, and p.L35P were also associated with greater sensitivity to olaparib (Fig. 4c) and cisplatin (Fig. 4d) than WT-PALB2.

      AssayResult: 0.01 µM: 65; 0.08 µM: 50; 0.8 µM: 30; 8 µM: 20

      AssayResultAssertion: Abnormal

      Approximation: Exact Olaparib concentrations and assay result values not reported; values estimated from Figures 4a and 4c.

    5. Cells reconstituted with WT-PALB2 showed substantially less sensitivity to olaparib than cells expressing p.A1025R and p.I944N (Fig. 4a). Similar results were observed for cisplatin treatment, although the difference in sensitivity was less pronounced (Fig. 4b). p.L24S, p.L1070P, and p.L35P were also associated with greater sensitivity to olaparib (Fig. 4c) and cisplatin (Fig. 4d) than WT-PALB2.

      AssayResult: 0.01 µM: 50; 0.08 µM: 40; 0.8 µM: 20; 8 µM: 15

      AssayResultAssertion: Abnormal

      Approximation: Exact Olaparib concentrations and assay result values not reported; values estimated from Figures 4a and 4c.

    6. 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

      AssayResultAssertion: Normal

      StandardErrorMean: 0.58

    7. 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.101G>A p.(Arg34His)

    1. SUPPLEMENTARY DATA

      AssayResult: 34

      AssayResultAssertion: Abnormal

      PValue: < 0.0001

    2. SUPPLEMENTARY DATA

      AssayResult: 68

      AssayResultAssertion: Indeterminate

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    3. SUPPLEMENTARY DATA

      AssayResult: 90

      AssayResultAssertion: Normal

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    4. SUPPLEMENTARY DATA

      AssayResult: 46

      AssayResultAssertion: Indeterminate

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    5. SUPPLEMENTARY DATA

      AssayResult: 23.6

      AssayResultAssertion: Abnormal

      PValue: < 0.0001

    6. SUPPLEMENTARY DATA

      AssayResult: 82

      AssayResultAssertion: Normal

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    7. SUPPLEMENTARY DATA

      AssayResult: 53

      AssayResultAssertion: Indeterminate

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    8. SUPPLEMENTARY DATA

      AssayResult: 41

      AssayResultAssertion: Indeterminate

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    9. SUPPLEMENTARY DATA

      AssayResult: 95

      AssayResultAssertion: Normal

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    10. SUPPLEMENTARY DATA

      AssayResult: 90

      AssayResultAssertion: Normal

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    11. SUPPLEMENTARY DATA

      AssayResult: 83

      AssayResultAssertion: Not reported

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    12. SUPPLEMENTARY DATA

      AssayResult: 77

      AssayResultAssertion: Indeterminate

      PValue: < 0.01

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    13. SUPPLEMENTARY DATA

      AssayResult: 81

      AssayResultAssertion: Not reported

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    14. SUPPLEMENTARY DATA

      AssayResult: 38

      AssayResultAssertion: Abnormal

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    15. SUPPLEMENTARY DATA

      AssayResult: 5

      AssayResultAssertion: Abnormal

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    16. SUPPLEMENTARY DATA

      AssayResult: 36

      AssayResultAssertion: Abnormal

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    17. SUPPLEMENTARY DATA

      AssayResult: 85

      AssayResultAssertion: Not reported

      PValue: Not reported

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    18. SUPPLEMENTARY DATA

      AssayResult: 58

      AssayResultAssertion: Indeterminate

      PValue: < 0.0001

      Approximation: Exact assay result value not reported; value estimated from Figure 6C.

    19. SUPPLEMENTARY DATA

      AssayResult: 86.74

      AssayResultAssertion: Not reported

      PValue: 0.1836

      Comment: Exact values reported in Table S3.

    20. 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.11C>T p.(Pro4Leu)

    1. Source Data

      AssayResult: 128.59

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 14.72

      Comment: Exact values reported in “Source Data” file.

    2. Source Data

      AssayResult: 84.05

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 16.48

      Comment: Exact values reported in “Source Data” file.

    3. Source Data

      AssayResult: 97.73

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 5.41

      Comment: Exact values reported in “Source Data” file.

    4. Source Data

      AssayResult: 19.53

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 8.56

      Comment: Exact values reported in “Source Data” file.

    5. Source Data

      AssayResult: 119.03

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 6.12

      Comment: Exact values reported in “Source Data” file.

    6. Source Data

      AssayResult: 37.28

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 11.28

      Comment: Exact values reported in “Source Data” file.

    7. Source Data

      AssayResult: 111.51

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 7.63

      Comment: Exact values reported in “Source Data” file.

    8. Source Data

      AssayResult: 80.44

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 9.06

      Comment: Exact values reported in “Source Data” file.

    9. Source Data

      AssayResult: 27.29

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 6.53

      Comment: Exact values reported in “Source Data” file.

    10. Source Data

      AssayResult: 102.2

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 12.81

      Comment: Exact values reported in “Source Data” file.

    11. Source Data

      AssayResult: 112.08

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 4.1

      Comment: Exact values reported in “Source Data” file.

    12. Source Data

      AssayResult: 87.4

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 0.88

      Comment: Exact values reported in “Source Data” file.

    13. Source Data

      AssayResult: 100.97

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 7.27

      Comment: Exact values reported in “Source Data” file.

    14. Source Data

      AssayResult: 20.08

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 6.84

      Comment: Exact values reported in “Source Data” file.

    15. Source Data

      AssayResult: 89.72

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 7.95

      Comment: Exact values reported in “Source Data” file.

    16. Source Data

      AssayResult: 93.33

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 11

      Comment: Exact values reported in “Source Data” file.

    17. Source Data

      AssayResult: 83.16

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 0.2

      Comment: Exact values reported in “Source Data” file.

    18. Source Data

      AssayResult: 26.03

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 11.42

      Comment: Exact values reported in “Source Data” file.

    19. Source Data

      AssayResult: 72.7

      AssayResultAssertion: Not reported

      ReplicateCount: 3

      StandardErrorMean: 9.73

      Comment: Exact values reported in “Source Data” file.

    20. Source Data

      AssayResult: 97.61

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardDeviation: 0.97

      StandardErrorMean: 0.68

      Comment: Exact values reported in “Source Data” file.

    21. 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.10C>T p.(P4S)

    1. 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)

    2. we selected 73 previously unstudied variants: 63 suspected Brugada syndrome variants and 10 suspected benign variants

      HGVS: NM_198056.2:c.1045G>A p.(Asp349Asn)

  3. Feb 2021
    1. We analysed a total of 82 blood samples derived from 77 individuals (online supplemental table 3). These 77 individuals corresponded either to new index cases suspected to harbour a pathogenic TP53 variant or to relatives of index cases harbouring TP53 variants.

      HGVS: NM000546.5:c.(?-202)(29+1-28+1)del p.?

      Comment: A CAID could not be generated for this deletion variant with uncertain breakpoints.

    2. Supplemental material

      AssayResult: 6.4

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    3. Supplemental material

      AssayResult: 3.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details; The blood sample used to test this variant was derived from an individual carrying the c.723del variant in combination with the c.*1175A>C variant in heterozygosity.

    4. Supplemental material

      AssayResult: 5.5, 5.7

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details; The blood sample used to test this variant was derived from an individual carrying the variant in homozygosity.

    5. Supplemental material

      AssayResult: 20.5

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    6. Supplemental material

      AssayResult: 3.4

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    7. Supplemental material

      AssayResult: 2.6, 4.8

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    8. Supplemental material

      AssayResult: 3.8

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details; This variant was reported as c.323_235del but assumed to be c.323_325del, which corresponds to the reported protein change (p.(Gly108_Phe109delinsVal)).

    9. Supplemental material

      AssayResult: 4, 5

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    10. Supplemental material

      AssayResult: 5.8, 6.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    11. Supplemental material

      AssayResult: 5.3

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    12. Supplemental material

      AssayResult: 5.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    13. Supplemental material

      AssayResult: 17.1

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    14. Supplemental material

      AssayResult: 3.2

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    15. Supplemental material

      AssayResult: 3.5

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    16. Supplemental material

      AssayResult: 4.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    17. Supplemental material

      AssayResult: 2.9

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    18. Supplemental material

      AssayResult: 6.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    19. Supplemental material

      AssayResult: 12.9

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    20. Supplemental material

      AssayResult: 4.7

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    21. Supplemental material

      AssayResult: 7.1, 6.0

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    22. Supplemental material

      AssayResult: 3.1

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    23. Supplemental material

      AssayResult: 5.4

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    24. Supplemental material

      AssayResult: 5

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    25. Supplemental material

      AssayResult: 4.8

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    26. Supplemental material

      AssayResult: 3.8

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    27. Supplemental material

      AssayResult: 3.2

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    28. Supplemental material

      AssayResult: 58

      AssayResultAssertion: Normal

      Comment: See Table S2 for details

    29. Supplemental material

      AssayResult: 5.8

      AssayResultAssertion: Abnormal

      Comment: See Table S2 for details

  4. Jan 2020
  5. Dec 2019