Table 2.
RET Mutation Allele Counts in Non-TCGA ExAC
| RET Mutationa | Non-TCGA ExACb | 90% Penetrance | 50% Penetrance | ||||
|---|---|---|---|---|---|---|---|
| Allele Count | Alleles Observed | Minor Allele Frequency | Alleles Expectedc | P Valued | Alleles Expectedc | P Valued | |
| ATA moderate-risk level (MOD) | |||||||
| c.1799G > A:p.Arg600Gln | 80,494 | 3 | 3.73 × 10−5 | 2 | 4.79 × 10−1 | 3 | 1.00 × 10° |
| c.2330A > G:p.Asn777Ser | 105,944 | 1 | 9.44 × 10−6 | 3 | 2.48 × 10−1 | 4 | 1.34 × 10−1 |
| c.2370G > C:p.Leu790Phe | 105,414 | 1 | 9.49 × 10−6 | 3 | 2.48 × 10−1 | 4 | 1.34 × 10−1 |
| c.2370G > T:p.Leu790Phe | 105,414 | 2 | 1.90 × 10−5 | 3 | 5.64 × 10−1 | 4 | 3.17 × 10−1 |
| c.2410G > A:p.Val804Met | 55,798 | 11 | 1.97 × 10−4 | 2 | 1.96 × 10−10 | 3 | 3.86 × 10−6 |
| c.2410G > T:p.Val804Leu | 55,798 | 1 | 1.79 × 10−5 | 2 | 4.79 × 10−1 | 3 | 2.48 × 10−1 |
| c.2497C > T:p.Arg833Cys | 104,240 | 2 | 1.92 × 10−5 | 3 | 5.64 × 10−1 | 4 | 3.17 × 10−1 |
| c.2531G > A:p.Arg844Gln | 105,686 | 4 | 3.78 × 10−5 | 3 | 5.64 × 10−1 | 4 | 1.00 × 10° |
| c.2735G > C:p.Arg912Pro | 106,202 | 1 | 9.42 × 10−6 | 3 | 2.48 × 10−1 | 4 | 1.34 × 10−1 |
| ATA high-risk level (H) | |||||||
| c.1900T > C:p.Cys634Arg | 106,030 | 1 | 9.43 × 10−6 | 3 | 2.48 × 10−1 | 4 | 1.34 × 10−1 |
| c.1901G > T:p.Cys634Phe | 106,036 | 1 | 9.43 × 10−6 | 3 | 2.48 × 10−1 | 4 | 1.34 × 10−1 |
Fifty ATA pathogenic RET single nucleotide variants, not observed in non-The Cancer Genome Atlas Exome Aggregation Consortium (TCGA ExAC), collapsed by residue: moderate-risk level: p.G533C, p.K603E, p.T606C, p.C609S/R/G/T/F, p.C611S/R/G/T/F/W, p.C618S/R/G/T/F/W, p.C620S/R/G/T/F/W, p.C630S/R/T/F, p.D631T p.K666E, p.E768D, p.E768D, p.Val804L, p.S891A; high-risk level: p.C634S/G/T/W, p.A883F; highest-risk level: p.E805K, p.T806C, p.M918T. Annotated using Reference Sequence accession NM_020975.
Non-TCGA ExAC data for ∼51,000 individuals. The age of individuals included in this dataset, at the time of ascertainment, ranges from 18 to 85, with most individuals aged 40 to 70 y.
Calculated using the method of Whiffin et al. (14). MTC lifetime risk estimated at one in 3000, genetic heterogeneity is estimated at 20%, allelic heterogeneity at 25%, and powered for penetrance >90% and >50%.
One-way χ2 test to compare observed and expected values using a Bonferroni corrected P value threshold for significance for performing 61 tests (P value threshold = 8.2 × 10−5).