Table 3 Evaluation of the impact of the detected TP53 and ARID1A mutations based on databases, in silico prediction pipeline, immunohistochemistry and functional assay.
Gene | Variant | exon | VAF % | Type | ClinVar | Cosmic | in silico‡ prediction | IHC§ | Functional assays | Overall evaluated pathogenicity |
|---|---|---|---|---|---|---|---|---|---|---|
ARID1A | p.Q583X | 3 | 14 | nonsense | novel | novel | NA | 10 | NA | pathogenic |
p.Q1188X†| 14 | 18 | nonsense | novel | pathogenic | NA | 5 | NA | pathogenic | |
p.K1230Mfs | 14 | 22 | fs | novel | novel | NA | 25 | NA | pathogenic | |
p.P1618S†| 18 | 22 | missense | novel | pathogenic | benign (5/14) | 5 | NA | likely pathogenic | |
p.R1721X | 20 | 19 | nonsense | novel | pathogenic | NA | <1 | NA | pathogenic | |
p.E1779G | 20 | 46 | missense | NA | novel | benign (1/14) | 80 | NA | likely benign | |
p.Q1894X | 20 | 61 | nonsense | novel | pathogenic | NA | 3 | NA | pathogenic | |
p.V2244G | 20 | 18 | missense | novel | pathogenic | benign (6/14) | 30 | NA | likely pathogenic | |
TP53 | p.P80S | 4 | 29 | missense | VUS | novel | benign (4/14) | wt | wt | likely benign |
p.L194P | 6 | 76 | missense | VUS | novel | patho (11/14) | aberrant | deleterious | pathogenic | |
p.R196X | 6 | 6 | nonsense | pathogenic | pathogenic | NA | wt | NA | pathogenic | |
p.R273P | 8 | 62 | missense | patho/likely patho | novel | patho (12/14) | aberrant | deleterious | pathogenic | |
p.G245D | 7 | 70 | missense | patho/likely patho | novel | patho (12/14) | aberrant | deleterious | pathogenic | |
p.R280K | 8 | 60 | missense | VUS | novel | patho (12/14) | aberrant | deleterious | pathogenic | |
c.75–1G>T | i2 | 19 | splice | novel | novel | NA | wt + aberrant clone | NA | likely pathogenic | |
c.782 + 1G>C | i7 | 16 | splice | novel | pathogenic | NA | wt | NA | likely pathogenic | |
c.919 + 1G>A | i8 | 60 | splice | novel | pathogenic | NA | wt | NA | likely pathogenic |
