TABLE 3.
Overview of all CTNNB1 pathogenic variants identified in our cohort
| Patient | Genomic position | cDNA position | Protein position | Exon | Variant type | Inheritance | ACMG classification | Reported variant |
|---|---|---|---|---|---|---|---|---|
| P1 | chr3:41266700 | c.495 + 2dup | splice variant | Intron 4 | Splicing | De novo | Likely pathogenic | Novel |
| P2 | chr3:41277893–41,277,894 | c.1857_1858del | p.(Cys619*) | 12 | Nonsense | De novo | Pathogenic | Novel |
| P3 | chr3:41274904 | c.1154dup | p.(Arg386Glnfs*9) | 8 | Frameshift | De novo | Pathogenic | Novel |
| P4 | chr3:41277290 | c.1759C > T | p.(Arg587*) | 11 | Nonsense | De novo | Pathogenic | Reported |
| P5 | chr3:41277290 | c.1759C > T | p.(Arg587*) | 11 | Nonsense | De novo | Pathogenic | Reported |
| P6 | chr3:41275328 | c.1494dup | p.(His499Thrfs*31) | 9 | Frameshift | De novo | Pathogenic | Reported |
| P7 | chr3:41267150 | c.735‐1G > T | Splice variant | Intron 5 | Splicing | De novo | Pathogenic | Novel |
| P8 | chr3:41266471 | c.268C > T | p.(Arg90*) | 4 | Nonsense | De novo | Pathogenic | Reported |
| P9 | chr3:41266502–41,266,503 | c.299_300del | p.(Pro100Argfs*5) | 4 | Frameshift | De novo | Pathogenic | Novel |
| P10 | chr3:41268761 | c.999C > A | p.(Tyr333*) | 7 | Nonsense | De novo | Pathogenic | Reported |
| P11 | chr3:41268749 | c.987dup | p.(Thr330Aspfs*23) | 7 | Frameshift | De novo | Pathogenic | Novel |
| P12 | chr3:41266486 | c.283C > T | p.(Arg95*) | 4 | Nonsense | De novo | Pathogenic | Reported |
| P13 | chr3:41277879 | c.1843dup | p.(Ala615Glyfs*6) | 12 | Frameshift | De novo | Pathogenic | Novel |
| P14 | chr3:41278134 | c.2010del | p.(Tyr670*) | 13 | Nonsense | De novo | Pathogenic | Novel |
| P15 | chr3:41267347 | c.931del | p.(Ser311Alafs*14) | 6 | Frameshift | De novo | Pathogenic | Novel |
| P16 | chr3:41277291–41,277,292 | c.1760_1761del | p.(Arg587Hisfs*21) | 11 | Frameshift | De novo | Pathogenic | Novel |
| P17 | chr3:41277889 | c.1853dup | p.(Cys619Leufs*2) | 12 | Frameshift | De novo | Pathogenic | Novel |
| P18 | chr3:41268712 | c.950del | p.(Ala317Valfs*8) | 7 | Frameshift | De novo | Pathogenic | Novel |
| P19 | chr3:41277220–41,277,221 | c.1689_1690dup | p.(Val564Glyfs*7) | 11 | Frameshift | De novo | Pathogenic | Novel |
| P20 | chr3:41266444 | c.242‐1G > C | Splice variant | Intron 3 | Splicing | NK | Likely pathogenic | Reported |
| P21 | chr3:41279528 | c.2098dup | p.(Ile700Asnfs*14) | 14 | Frameshift | De novo | Pathogenic | Novel |
| P22 | chr3:41275254 | c.1420C > T | p.(Arg474*) | 9 | Nonsense | De novo | Pathogenic | Reported |
| P23 | chr3:41266471 | c.268C > T | p.(Arg90*) | 4 | Nonsense | NK | Pathogenic | Reported |
| P24 | chr3:41266471 | c.268C > T | p.(Arg90*) | 4 | Nonsense | NK | Pathogenic | Reported |
Note: Genomic, cDNA, and protein position are given as well as affected exons. All genomic positions are based on CRCh37/hg19; CTNNB1 reference sequence is NM_001904.4; NK, not known; *, the stop codon; ACMG, American College of Medical Genetics and Genomic.