Table 1.
Highlighted damaging and novel variants in cutaneous squamous cell carcinoma (cSCC)
| Gene | Chromosome | HGVS DNA reference | HGVS protein reference | Variant type | Predicted effect | dbSNP | COSMIC | ExAC | ClinVar | Novel | Genotype | Patient 1 | Patient 2 | Patient 3 | Reactome pathway |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BPI | 20 | g.36938975G > A | ENSENSP00000262865: p.Gly157Ser | Single AA change | Deleterious/damaging | None | None | None | No match | Yes | Heterozygous | X | - | - | R-HSA-6798695 |
| BPI | 20 | g.36954682C > T | ENSENSP00000262865: p.Pro341Ser | Single AA change | Deleterious/damaging | None | None | None | No match | Yes | Heterozygous | - | - | X | R-HSA-6798696 |
| HRAS | 11 | g.534286C > G | ENSENSP00000309845: p.Gly13Arg | Single AA change | Deleterious/damaging | rs104894228 | None | None | HRAS13GR pathogenic/likely pathogenic | No | Heterozygous | - | X | - | R-HSA-2682334 |
| HRAS | 11 | g.534285C > T | ENSENSP00000309845: p.Gly13Asp | Single AA change | Deleterious/damaging | rs104894226 | CDS = c.38G > A; AA = p.G13D, | None | HRAS13GD pathogenic | No | Heterozygous | - | - | X | R-HSA-2682335 |
| EPHA7 | 6 | g.93956676G > A | ENSENSP00000358309: p.Arg854Cys | Single AA change | Deleterious/Damaging | None | None | None | No match | Yes | Heterozygous | X | - | - | R-HSA- 2682336 |
| EPHA7 | 6 | g.93953241C > T | ENSENSP00000358309: p.Gly967Glu | Single AA change | Deleterious/damaging | None | None | None | No match | Yes | Heterozygous | - | X | - | R-HSA- 2682337 |
| TP53 | 17 | g.7577085C > T | ENSENSP00000269305: p.Glu285Lys | Single AA change | Deleterious/damaging | rs112431538 | CDS = c.853G > A; AA = p.E285K, | None | TP53285EK pathogenic/likely pathogenic, drug response | No | Heterozygous | X | - | - | NA |
| TP53 | 17 | g.7577099C > T | ENSENSP00000269305: p.Arg280Lys | Single AA change | Deleterious/damaging | None | CDS = c.839G > A; AA = p.R280K, | None | TP53280RK conflicting interpretations of pathogenicity | No | Heterozygous | - | X | - | NA |
| TP53 | 17 | g.7577538C > T | ENSENSP00000269305: p.Arg248Gln | Single AA change | Deleterious/damaging | rs11540652 | CDS = c.743G > A; AA = p.R248Q, CDS = c.464G > A; AA = p.R155Q, | 5.77E-05 | TP53248RQ pathogenic/likely pathogenic | No | Heterozygous | - | - | X | NA |
| TP53 | 17 | g.7578526C > T | ENSENSP00000269305: p.Cys135Tyr | Single AA change | Deleterious/damaging | None | CDS = c.125G > A; AA = p.C42Y, CDS = c.404G > A; AA = p.C135Y, CDS = c.8G>A; AA = p.C3Y, | None | TP53135CY likely pathogenic | No | Heterozygous | - | - | X | NA |
Whole-exome sequencing (Illumina Hi-Seq) was performed on the three cases of collected samples with a median coverage of 209×–213×. DNA mutations were called relative to matched patient blood. Genes within the neutrophil degranulation and Eph-ephrin pathways were selected for this table if they met any of the following criteria: multiple novel mutations within a single sample, novel mutations spanning multiple samples, or mutations matching known health related phenotypes, including cancer.