Table 2.
TP63 variants identified in affected individuals and controls using molecular inversion probes (MIPs) sequencing
| Genomic location at chr3 | Variant cDNA | Amino-acid change | Inheritance | Protein domain | SIFT (class; score) | Grantham score | CADD PHRED-like score | Phenotype(s) | dbSNP ID | ExAC frequency |
|---|---|---|---|---|---|---|---|---|---|---|
| Affected individuals | ||||||||||
| g.189526303_189526310del | c.569_576del | p.(Ala190Aspfs*5) | Paternal | DBD | – | – | 34 | CLA (left) | – | – |
| g.189582111G>A | c.670G>A | p.(Val224Ile) | Paternal | DBD | Deleterious; 0 | 29 | 17.6 | CLP (bilateral) | rs757669482 | 0.000008 |
| g.189586373C>T | c.997C>T | p.(Gln333*) | NA | DBD | – | – | 29.1 | CLP (bilateral) | – | – |
| g.189590648G>A | c.1213G>A | p.(Val405Met) | Paternal | OD | Deleterious; 0.01 | 21 | 18.04 | CLA (left) | – | – |
| g.189590658G>A | c.1223G>A | p.(Arg408His) | Paternal | OD | Deleterious; 0 | 29 | 28.3 | CLP (CL and alveolus left, split velum and uvula) | rs751698974 | 0.000008 |
| g.189597893C>T | c.1390C>Ta | p.(Arg464Trp)a | Maternal | – | Deleterious; 0 | 101 | 15.76 | CLP (left) | rs369826042 | 0.00004 |
| g.189604292C>T | c.1459C>T | p.(Arg487Cys) | Maternal | TA2 | Deleterious; 0 | 180 | 21.4 | CLP | rs777306829 | 0.0001 |
| Controls | ||||||||||
| g.189455551T>G | c.85T>G | p.(Phe29Val) | – | TA | Tolerated; 0.05 | 50 | 17.1 | – | rs533808847 | 0.000008 |
| g.189526142A>G | c.406A>G | p.(Thr136Ala) | – | DBD | Tolerated; 0.08 | 58 | 17.48 | – | – | – |
| g.189582166A>G | c.725A>G | p.(Lys242Arg) | – | DBD | Deleterious; 0 | 26 | 15.77 | – | rs201617537 | – |
| g.189586497C>T | c.1121C>T | p.(Thr374Met) | – | DBD | Deleterious; 0 | 81 | 19.14 | – | rs199807776 | 0.00005 |
acDNA annotation is based on the transcript NM_003722.4 except for the variant in gamma isoform (p.(Arg464Trp)), which is based on NM_001114979.1. Human genome reference hg19 was used for annotation. Exons in transcript NM_003722.4 are numbered 1–14 (i.e., excluding exons 10a and 10ʹ), whereas NM_001114979.1 contains exons 1–10 and exon 10ʹ (i.e., excluding exons 10a and 11–14) (see Fig. 1)