Table 1.
The three de novo variants validated by Sanger Sequencing.
| Gene | TNC | IGFALS | CREBBP |
|---|---|---|---|
| Chromosome | chr9 | chr16 | chr16 |
| Position | 117852975 | 1841118 | 3823901 |
| Reference Allele | C | G | C |
| Alternative Allele | T | A | – |
| Mutation Type | Missense | Missense | Frameshift |
| Sequence Variant | c.323G>A | c.1415C>T | c.2199delG |
| Protein Variant | p.Arg108His | p.Ala472Val | p.Gln733Hisfs*5 |
| phyloP Score | 2.369 | 0.598 | 1.492 |
| GERP Score | 1200.8 | 2536.4 | 476.2 |
| SIFT Score | 0 | 0.30 | – |
| Mutation Assessor | 1.87 | 0.995 | – |
| Classification 1 | Likely pathogenic 2 | Variants of unknown significance | Pathogenic |
1 Variant Classification is based on the recommendations of Ambry Genetics, but pathogenicity of de novo variants in TNC and IGFALS are not certain; 2 TNC c.323G>A is reported in dbSNP as rs151119387, but MAF/MinorAlleleCount = 0.0002/1. Overall MAF in 1000 genomes, ESP6500, ExAc database is less than 0.0003. TNC: Tenascin C; IGFALS: Insulin-like growth factor-binding protein, acid labile subunit; CREBBP: CREB (cAMP response element-binding protein) binding protein; phyloP: Phylogenetic p-values; GERP: Genomic evolutionary rate profiling; SIFT: Sorting intolerant from tolerant.