7 Matching Annotations
  1. Mar 2021
    1. 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: 4.9

      AssayResultAssertion: Normal

      StandardErrorMean: 0.01

    2. 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.3356T>C p.(Leu1119Pro)

    1. Source Data

      AssayResult: 17.5

      AssayResultAssertion: Abnormal

      ReplicateCount: 2

      StandardErrorMean: 7.75

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

    2. Source Data

      AssayResult: 7.42

      AssayResultAssertion: Abnormal

      ReplicateCount: 2

      StandardDeviation: 2.87

      StandardErrorMean: 2.03

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

    3. 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.688G>T p.(E230X)

    1. 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)

    2. 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)