Table 2 Variants for which reclassification resulted in a downgrade in reporting category

From: The impact of variant classification on the clinical management of hereditary cancer syndromes

Family

Gene

 Variant

History, gender (age at reclassification)

Classification downgrades

Changes in management

1

TP53

c.800G>A (p.R267Q)

Breast cancer at 53; Fam hx breast & sarcoma, F (54)

LP→VUS

O, C

2

BRCA1

c.594-2A>C (p.?)

40 yo with colon cancer, M (41)

LP→VUS

#

3

BRCA2

c.9699_9702delTATG (p.Cys3233TrpfsX15)

Bilateral breast cancer at 46 & 65; fam hx of breast, F (87)

P→VUS

O,C

   

Melanomas at 40 & 50; Family history of BRCA2 pathogenic variant, F (63)

P→VUS

S,C

4

CHEK2

c.1312G>T (p.Asp438Tyr)

Thyroid+synchronous head/neck cancer at 66; adenomatous colon polyps >10, F (48)

P→VUS

C

5

TP53

c.709A>G(p.Met237Val)

Bilateral breast cancer at 22 and 41, F (52)

P→VUS

O, C

  1. VUS variant of uncertain significance, LP likely pathogenic, P pathogenic, O organ surveillance, S surgical recommendations, C cascade testing, # patient deceased at time of reclassification, F female, M male
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