Table 2.
Characteristics of the 11 Deleterious Somatic Mutations in the HPD Tumors after Anti-PD-1 Treatment
| Gene | Genomic Positiona | Genomic Mutation | Exon | Protein Alteration | Predicted Effect of Somatic Mutation |
snp137 | ESP MAFf | |||
|---|---|---|---|---|---|---|---|---|---|---|
| SIFTb | PolyPhen-2c | FATHMMd | GERP++e | |||||||
| TRPC4 | chr13: 38211734 | c.G2045A | 10 | p.R682H | Deleterious (0.00) | Probably damaging (0.999) | Potentially associated with cancer (−2.83) | 6.06 | NA | NA |
| POTEE | chr2: 132021334 | c.A2306T | 15 | p.Y769F | Deleterious (0.00) | Probably damaging (0.997) | Potentially associated with cancer (−4.69) | NA | NA | NA |
| FBN2 | chr5: 127666313 | c.C4297T | 33 | p.R1433C | Deleterious (0.00) | Probably damaging (0.983) | Potentially associated with cancer (−2.9) | 4.21 | NA | 7.70 × 10−5 |
| KMT2C | chr7: 151932981 | c.G2690C | 16 | p.R897P | Deleterious (0.00) | Probably damaging (0.995) | Potentially associated with cancer (−2.21) | 5.1 | NA | NA |
| FUT10 | chr8: 33246817 | c.G876T | 4 | p.K292N | Deleterious (0.00) | Probably damaging (1.00) | Potentially associated with cancer (−4.75) | 3.42 | NA | NA |
| PQBP1 | chrX: 48759773 | c.C256T | 4 | p.P86S | Deleterious (0.00) | Probably damaging (0.996) | Potentially associated with cancer (−1.13) | 5.02 | NA | NA |
| TSC2 | chr16: 2137907 | c.A4832C | 37 | p.Y1611S | Deleterious (0.02) | Probably damaging (0.997) | Potentially associated with cancer (−3.16) | 4.59 | NA | NA |
| MFSD6 | chr2: 191301728 | c.G973A | 3 | p.G325R | Deleterious (0.00) | Probably damaging (0.998) | Potentially associated with cancer (−2.42) | 6.07 | NA | NA |
| CYP2D6 | chr22: 42522990 | c.C1025T | 7 | p.T342M | Deleterious (0.00) | Probably damaging (0.996) | Potentially associated with cancer (−2.26) | 4.06 | NA | NA |
| VHL | chr3: 10191479 | c.C349G | 2 | p.L117V | Deleterious (0.00) | Probably damaging (0.994) | Potentially associated with cancer (−6.95) | 3.07 | NA | NA |
| RAD54B | chr8: 95411747 | c.T721G | 6 | p.F241V | Deleterious (0.01) | Probably damaging (0.996) | Potentially associated with cancer (−3.01) | 5.55 | NA | NA |
ESP, NHLBI Exome Sequencing Project; NA, not available. See also Figure S3.
Genomic positions are given according to the UCSC Genome Browser hg19 reference assembly.
SIFT scores range from 0 to 1. The amino acid substitution is predicted to be damaging if the score is ≤0.05 and tolerated if the score is >0.05.
PolyPhen-2 scores 0.85–1 are interpreted as probably damaging, scores 0.2–0.85 are possibly damaging, and sores 0–0.2 are benign.
Predictions with FATHMM scores less than 0.75 indicate that the mutation is potentially associated with cancer; otherwise the mutation is not associated with cancer.
There is an indication of evolutionary conservation if a given site shows a GERP++ score >2.
MAFs are according to the NHLBI GO Exome Sequencing Project (ESP6500SI-V2 release) Exome Variant Server v.0.0.21 (August 2013).