1,045 Matching Annotations
  1. Mar 2021
    1. Partial or complete loss-of-function variants in SCN5A are the most common genetic cause of the arrhythmia disorder Brugada syndrome (BrS1).

      Gene: SCN5A

      Disease: Brugada syndrome

      MONDO: MONDO:0011001

      InheritancePattern: Autosomal dominant

    2. High-Throughput Reclassification of SCN5A Variants
    3. 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)

    4. 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)

    5. 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)

    6. 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).

    7. 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)

    8. 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)

    9. 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)

    10. 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)

    11. 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)

    12. 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)

    13. 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)

    14. 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)

    15. 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)

    16. 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)

    17. 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)

    18. 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)

    19. 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)

    20. 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)

    21. 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)

    22. 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)

    23. 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)

    24. 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)

    25. 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)

    26. 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)

    27. 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)

    28. 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)

    29. 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)

    30. 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)

    31. 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)

    32. 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)

    33. 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)

    34. 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)

    35. 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)

    36. 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)

    37. 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)

    38. 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)

    39. 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)

    40. 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)

    41. 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)

    42. 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)

    43. 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)

    44. 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)

    45. 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)

    46. 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)

    47. 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)

    48. 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)

    49. 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)

    50. 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)

    51. 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)

    52. 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)

    53. 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)

    54. 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)

    55. 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)

    56. 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)

    57. 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)

    58. 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)

    59. 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)

    60. 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)

    61. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 109.6

      AssayResultAssertion: Normal

      ReplicateCount: 11

      StandardErrorMean: 19.8

      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)

    62. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 117.8

      AssayResultAssertion: Normal

      ReplicateCount: 15

      StandardErrorMean: 14.5

      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)

    63. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 39

      AssayResultAssertion: Abnormal

      ReplicateCount: 16

      StandardErrorMean: 6.4

      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)

    64. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 119.6

      AssayResultAssertion: Normal

      ReplicateCount: 22

      StandardErrorMean: 19.5

      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)

    65. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 0.2

      AssayResultAssertion: Abnormal

      ReplicateCount: 15

      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)

    66. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 32.8

      AssayResultAssertion: Abnormal

      ReplicateCount: 16

      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)

    67. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 89.4

      AssayResultAssertion: Normal

      ReplicateCount: 26

      StandardErrorMean: 12.7

      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)

    68. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 85.1

      AssayResultAssertion: Normal

      ReplicateCount: 35

      StandardErrorMean: 10.6

      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)

    69. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 103.2

      AssayResultAssertion: Normal

      ReplicateCount: 33

      StandardErrorMean: 12.7

      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)

    70. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 120.5

      AssayResultAssertion: Normal

      ReplicateCount: 33

      StandardErrorMean: 13.6

      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)

    71. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 94.8

      AssayResultAssertion: Normal

      ReplicateCount: 33

      StandardErrorMean: 12.6

      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)

    72. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 109.1

      AssayResultAssertion: Normal

      ReplicateCount: 26

      StandardErrorMean: 14.8

      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)

    73. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 101

      AssayResultAssertion: Normal

      ReplicateCount: 41

      StandardErrorMean: 8.9

      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)

    74. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 104.3

      AssayResultAssertion: Normal

      ReplicateCount: 30

      StandardErrorMean: 16.3

      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)

    75. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 105.8

      AssayResultAssertion: Normal

      ReplicateCount: 36

      StandardErrorMean: 12.7

      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)

    76. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 103.2

      AssayResultAssertion: Normal

      ReplicateCount: 37

      StandardErrorMean: 21.8

      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)

    77. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 51.9

      AssayResultAssertion: Indeterminate

      ReplicateCount: 12

      StandardErrorMean: 18.8

      Comment: This variant had a mild loss of function in peak current (50-75% of wildtype). It had unmeasured late current, but has been previously reported to have high late current (GOF feature). Therefore it was considered to meet neither the abnormal or normal functional parameter. (Personal communication: A. Glazer)

    78. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 64.8

      AssayResultAssertion: Abnormal

      ReplicateCount: 31

      StandardErrorMean: 11.1

      Comment: This variant had a mild loss of function in peak current (50-75% of wildtype). It also had a very large increase in recovery from inactivation (>10-fold slower). Therefore it was considered to have a partial loss of function (in vitro function consistent with Brugada Syndrome). (Personal communication: A. Glazer)

    79. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 2.2

      AssayResultAssertion: Abnormal

      ReplicateCount: 16

      StandardErrorMean: 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)

    80. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 114.3

      AssayResultAssertion: Abnormal

      ReplicateCount: 16

      StandardErrorMean: 22.4

      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)

    81. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 23.2

      AssayResultAssertion: Abnormal

      ReplicateCount: 14

      StandardErrorMean: 7.1

      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)

    82. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 113

      AssayResultAssertion: Normal

      ReplicateCount: 17

      StandardErrorMean: 28.6

      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)

    83. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 0.1

      AssayResultAssertion: Abnormal

      ReplicateCount: 19

      StandardErrorMean: 0.1

      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)

    84. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 86.7

      AssayResultAssertion: Normal

      ReplicateCount: 28

      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)

    85. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 0.7

      AssayResultAssertion: Abnormal

      ReplicateCount: 17

      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)

    86. Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 115.6

      AssayResultAssertion: Normal

      ReplicateCount: 19

      StandardErrorMean: 24.7

      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)

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

      HGVS: NM_198056.2:c.5872C>T p.(Arg1958Ter)

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

      HGVS: NM_198056.2:c.5692C>T p.(Arg1898Cys)

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

      HGVS: NM_198056.2:c.5189C>A p.(Pro1730His)

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

      HGVS: NM_198056.2:c.5164A>G p.(Asn1722Asp)

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

      HGVS: NM_198056.2:c.5126C>T p.(Thr1709Met)

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

      HGVS: NM_198056.2:c.5038G>A p.(Ala1680Thr)

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

      HGVS: NM_198056.2:c.5015C>A p.(Ser1672Tyr)

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

      HGVS: NM_198056.2:c.4981G>A p.(Gly1661Arg)

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

      HGVS: NM_198056.2:c.4925G>A p.(Gly1642Glu)

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

      HGVS: NM_198056.2:c.4747C>T p.(Arg1583Cys)

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

      HGVS: NM_198056.2:c.4720G>A p.(Glu1574Lys)

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

      HGVS: NM_198056.2:c.4382C>G p.(Thr1461Ser)

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

      HGVS: NM_198056.2:c.4346A>G p.(Tyr1449Cys)

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

      HGVS: NM_198056.2:c.4283C>T p.(Ala1428Val)

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

      HGVS: NM_198056.2:c.4259G>T p.(Gly1420Val)

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

      HGVS: NM_198056.2:c.4258G>C p.(Gly1420Arg)

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

      HGVS: NM_198056.2:c.4217G>A p.(Gly1406Glu)

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

      HGVS: NM_198056.2:c.4213G>A p.(Val1405Met)

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

      HGVS: NM_198056.2:c.4213G>C p.(Val1405Leu)

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

      HGVS: NM_198056.2:c.4145G>T p.(Ser1382Ile)

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

      HGVS: NM_198056.2:c.4140C>A p.(Asn1380Lys)

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

      HGVS: NM_198056.2:c.4057G>A p.(Val1353Met)

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

      HGVS: NM_198056.2:c.4037T>C p.(Leu1346Pro)

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

      HGVS: NM_198056.2:c.4035G>T p.(Trp1345Cys)

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

      HGVS: NM_198056.2:c.3841G>T p.(Val1281Phe)

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

      HGVS: NM_198056.2:c.3784G>A p.(Gly1262Ser)

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

      HGVS: NM_198056.2:c.3727G>A p.(Asp1243Asn)

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

      HGVS: NM_198056.2:c.3673G>A p.(Glu1225Lys)

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

      HGVS: NM_198056.2:c.3040C>T p.(Pro1014Ser)

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

      HGVS: NM_198056.2:c.2783T>C p.(Leu928Pro)

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

      HGVS: NM_198056.2:c.2780A>G p.(Asn927Ser)

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

      HGVS: NM_198056.2:c.2701G>A p.(Glu901Lys)

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

      HGVS: NM_198056.2:c.2674T>A p.(Phe892Ile)

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

      HGVS: NM_198056.2:c.2635T>C p.(Trp879Arg)

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

      HGVS: NM_198056.2:c.2553C>A p.(Phe851Leu)

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

      HGVS: NM_198056.2:c.2516T>C p.(Leu839Pro)

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

      HGVS: NM_198056.2:c.2441G>A p.(Arg814Gln)

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

      HGVS: NM_198056.2:c.2422C>T p.(Arg808Cys)

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

      HGVS: NM_198056.2:c.2353G>A p.(Asp785Asn)

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

      HGVS: NM_198056.2:c.2317C>T p.(Pro773Ser)

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

      HGVS: NM_198056.2:c.2314G>A p.(Asp772Asn)

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

      HGVS: NM_198056.2:c.2291T>A p.(Met764Lys)

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

      HGVS: NM_198056.2:c.2236G>A p.(Glu746Lys)

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

      HGVS: NM_198056.2:c.2203G>A p.(Ala735Thr)

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

      HGVS: NM_198056.2:c.2204C>A p.(Ala735Glu)

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

      HGVS: NM_198056.2:c.2200A>G p.(Met734Val)

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

      HGVS: NM_198056.2:c.1186G>C p.(Val396Leu)

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

      HGVS: NM_198056.2:c.1156G>A p.(Gly386Arg)

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

      HGVS: NM_198056.2:c.1106T>A p.(Met369Lys)

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

      HGVS: NM_198056.2:c.1100G>T p.(Arg367Leu)

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

      HGVS: NM_198056.2:c.1099C>T p.(Arg367Cys)

    138. 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)

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

      HGVS: NM_198056.2:c.1038G>T p.(Glu346Asp)

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

      HGVS: NM_198056.2:c.1003T>C p.(Cys335Arg)

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

      HGVS: NM_198056.2:c.844C>T p.(Arg282Cys)

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

      HGVS: NM_198056.2:c.827T>A p.(Leu276Gln)

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

      HGVS: NM_198056.2:c.667G>C p.(Val223Leu)

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

      HGVS: NM_198056.2:c.533C>G p.(Ala178Gly)

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

      HGVS: NM_198056.2:c.525G>C p.(Lys175Asn)

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

      HGVS: NM_198056.2:c.407T>C p.(Leu136Pro)

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

      HGVS: NM_198056.2:c.327C>A p.(Asn109Lys)

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

      HGVS: NM_198056.2:c.278T>C p.(Phe93Ser)

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

      HGVS: NM_198056.2:c.250G>A p.(Asp84Asn)

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

      HGVS: NM_198056.2:c.5237C>T p.(Ala1746Val)

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

      HGVS: NM_198056.2:c.4109A>G p.(Asp1370Gly)

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

      HGVS: NM_198056.2:c.3835G>A p.(Val1279Ile)

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

      HGVS: NM_198056.2:c.3751G>A p.(Val1251Met)

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

      HGVS: NM_198056.2:c.2770G>A p.(Val924Ile)

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

      HGVS: NM_198056.2:c.2497G>A p.(Gly833Arg)

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

      HGVS: NM_198056.2:c.2141T>C p.(Val714Ala)

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

      HGVS: NM_198056.2:c.895T>A p.(Leu299Met)

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

      HGVS: NM_198056.2:c.856G>T p.(Ala286Ser)

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

      HGVS: NM_198056.2:c.496G>A p.(Ala166Thr)

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

      HGVS: NM_198056.2:c.5350G>A p.(Glu1784Lys)

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

      HGVS: NM_198056.2:c.4895G>A p.(Arg1632His)

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

      HGVS: NM_198056.2:c.4294A>G p.(Arg1432Gly)

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

      HGVS: NM_198056.2:c.3974A>G p.(Asn1325Ser)

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

      HGVS: NM_198056.2:c.2254G>A p.(Gly752Arg)

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

      HGVS: NM_198056.2:c.1859G>A p.(Arg620His)

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

      HGVS: NM_198056.2:c.1058C>T p.(Thr353Ile)

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

      HGVS: NM_198056.2:c.659C>T p.(Thr220Ile)

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

      HGVS: NM_198056.2:c.361C>T p.(Arg121Trp)

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

      HGVS: NM_198056.2:c.26G>T p.(Gly9Val)

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    1. affected boy (IV-1; 11 years)

      Case#: IV-1, male, 11 y.o, Pakistani

      DiseaseAssertion: Limb-girdle muscular dystrophy (LGMD2F), sarcoglycanopathy

      FamilyInfo: Consanguineous parents, both described as healthy and showing no abnormality. Three unaffected siblings were also reported: IV-2 (male, 10 y.o), IV-4 (male, 7 y.o), and IV-5 (female, 1.5 y.o). A deceased sister is included on the pedigree, but no details about this individual were reported. See Figure 1.

      CasePresentingHPOs: HP:0001288, HP:0002650, HP:0003547, HP:0003749, HP:0001655

      CaseHPOFreeText: Reduced weight gain noted at 3-4 y.o. Mild cardiac hypertrophy observed on cardiac review (additional echocardiography results reported in "Echocardiography" section). Additional phenotypic information reported in Supplementary Table 1.

      CaseNotHPOs: HP:0009077, HP:0000703, HP:0001382, HP:0000365, HP:0001510, HP:0001249, HP:0000478, HP:0030148, HP:0011675

      CaseNotHPOFreeText: Extensor muscles of the wrist, toes flexors, and hip abductors noted to be relatively normal. Additional phenotypic information reported in Supplementary Table 1.

      MotorAchievement: Sat without assistance at 8 months of age, walked at 15 months of age, ran at 1.5 months of age. Never jumped or hopped. Frequent falls noted, as well as difficulty in walking and climbing stairs since 3 y.o.

      CreatineKinase: 18SU (normal: 20SU for children, 10SU for adults) (see Supplementary Table 1). No assertion was made by the authors regarding whether this represents a normal or decreased CK level.

      PreviousTesting: Thyroid stimulating hormone: 2.3mU/L (normal: <0.6mU/L); Serum VZV IgG: 286mlU/ml (normal: >150mlU/ml); IGF-1:186 ng/μl (normal: 102-520 ng/μl for males, 14 y.o); PRL: 202 ng/dl (normal: 42.5-414 ng/dl for males); Vitamin D: 47nmol/L (normal: 25-50 nmol/L); Free T4: 17.0 pmol/L (normal:10.8-19.0 pmol/L) (see Supplementary Table 1)

      GenotypingMethod: (1) Targeted next generation sequencing of 31 genes associated with LGMD from proband genomic DNA extracted from peripheral blood sample; (2) Sanger sequencing of genomic DNA extracted from peripheral blood samples to confirm SGCD variant of interest in proband and three family members (III-3, III-4, IV-4). Variant was identified in homozygosity in the proband, in heterozygosity in each of the parents, and was not present in the unaffected sibling (IV-4).

      Variant: NM_000337.5:c.289C>T (p.Arg97Ter)

      CAID: CA3530549

      gnomAD: Not reported

  2. Feb 2021
    1. Supplemental material

      AssayResult: 111

      AssayResultAssertion: Normal

      ControlType: Normal, wild type TP53

      Comment: See Table S3 for details

    2. 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: NM_000546.5:c.844C>T p.(Arg282Trp)

    3. 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: NM_000546.5:c.736A>G p.(Met246Val)

    4. 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: NM_000546.5:c.638G>A p.(Arg213Gln)

    5. 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: NM_000546.5:c.535C>T p.(His179Tyr)

    6. 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.

    7. Supplemental material

      AssayResult: 69, 73

      AssayResultAssertion: Normal

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

    8. Supplemental material

      AssayResult: 100

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    9. Supplemental material

      AssayResult: 95

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    10. Supplemental material

      AssayResult: 80, 99

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    11. Supplemental material

      AssayResult: 94

      AssayResultAssertion: Normal

      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)).

    12. Supplemental material

      AssayResult: 101, 106

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    13. Supplemental material

      AssayResult: 89, 90

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    14. Supplemental material

      AssayResult: 88

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    15. Supplemental material

      AssayResult: 79

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    16. Supplemental material

      AssayResult: 78

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    17. Supplemental material

      AssayResult: 90

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    18. Supplemental material

      AssayResult: 86

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    19. Supplemental material

      AssayResult: 78

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    20. Supplemental material

      AssayResult: 83

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    21. Supplemental material

      AssayResult: 82

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    22. Supplemental material

      AssayResult: 86

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    23. Supplemental material

      AssayResult: 118

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    24. Supplemental material

      AssayResult: 62

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    25. Supplemental material

      AssayResult: 56, 52

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    26. Supplemental material

      AssayResult: 61

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

    27. Supplemental material

      AssayResult: 101

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    28. Supplemental material

      AssayResult: 98

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    29. Supplemental material

      AssayResult: 102

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

    30. Supplemental material

      AssayResult: 81

      AssayResultAssertion: Normal

      Comment: See Table S3 for details