Table 5 List of highly recurrent GENIE variants (≥ 6 samples) that are underrepresented in COSMIC (< 3 samples)

MET

p.A179T

c.535G > A

Non-Small Cell Lung Cancer(13);Melanoma(2);Colorectal Cancer(4)

ERBB3

p.E928G

c.2783A > G

Melanoma(1);Colorectal Cancer(2);Bladder Cancer(2);Hepatobiliary Cancer(1);Small Bowel Cancer(1);Breast Cancer(6);Esophagogastric Cancer(1)

CDKN2A

p.P75S

c.223C > T

Prostate Cancer(1);Colorectal Cancer(2);Ovarian Cancer(5);Non-Small Cell Lung Cancer(1);Endometrial Cancer(2);Breast Cancer(1);Cervical Cancer(1)

SMO

p.L23dup

c.67_69dupCTG

Thyroid Cancer(1);Melanoma(1);Glioma(2);Leukemia(2);Non-Small Cell Lung Cancer(2);Cancer of Unknown Primary(1);Endometrial Cancer(1);Breast Cancer(1)

SMARCA4

p.R1189Q

c.3566G > A

Glioma(1);Bladder Cancer(3);Renal Cell Carcinoma(1);Cancer of Unknown Primary(1);Breast Cancer(1);Esophagogastric Cancer(1)

CDKN2A

p.E69G

c.206A > G

Non-Small Cell Lung Cancer(6);Colorectal Cancer(1)

ERBB3

p.M91I

c.273G > A

Bladder Cancer(6);Endometrial Cancer(1)

ERBB3

p.K329E

c.985A > G

Bladder Cancer(4);Breast Cancer(1);Colorectal Cancer(1);Esophagogastric Cancer(1)

ERCC2

p.N238S

c.713A > G

Bladder Cancer(5);Breast Cancer(2)

FANCA

p.K1283R

c.3848A > G

Bladder Cancer(1);Endometrial Cancer(1);Hepatobiliary Cancer(1);Breast Cancer(3);Leukemia(1)

FLT1

p.R501K

c.1502G > A

Melanoma(1);Ovarian Cancer(1);Non-Small Cell Lung Cancer(2);Cancer of Unknown Primary(1);Breast Cancer(1);Cervical Cancer(1)

FLT4

p.P30fs

c.88delC

Non-Small Cell Lung Cancer(1);Colorectal Cancer(6)

IKZF1

p.D22N

c.64G > A

Colorectal Cancer(1);Non-Small Cell Lung Cancer(1);Melanoma(3);Glioma(1);Embryonal Tumor(1)

KDR

p.S265 L

c.794C > T

Myelodysplasia(1);Melanoma(1);Colorectal Cancer(1);Sellar Tumor(1);Non-Small Cell Lung Cancer(2);“Skin Cancer, Non-Melanoma”(1)

PIK3CB

p.R604fs

c.1809dupC

Bladder Cancer(1);“Skin Cancer, Non-Melanoma”(1);Breast Cancer(3);Endometrial Cancer(1);Esophagogastric Cancer(1)

APC

p.T1160K

c.3479C > A

Ovarian Cancer(1);Salivary Gland Cancer(1);Non-Small Cell Lung Cancer(1);Melanoma(1);Colorectal Cancer(2)

ARID1A

p.S735 N

c.2204G > A

Bladder Cancer(1);Hepatobiliary Cancer(1);Leukemia(1);Non-Small Cell Lung Cancer(1);Breast Cancer(1);Cervical Cancer(1)

ASXL1

p.S1028 L

c.3083C > T

Thyroid Cancer(1);Non-Small Cell Lung Cancer(2);Melanoma(1);Small Cell Lung Cancer(1);Prostate Cancer(1)

ATRX

p.G1071R

c.3211G > A

Skin Cancer, Non-Melanoma(1);Non-Small Cell Lung Cancer(2);Breast Cancer(1);Colorectal Cancer(1);Myeloproliferative Neoplasm(1)

BRCA1

p.E597K

c.1789G > A

Bladder Cancer(2);“Skin Cancer, Non-Melanoma”(1);Non-Small Cell Lung Cancer(1);Breast Cancer(1);Colorectal Cancer(1)

CARD11

p.R377Q

c.1130G > A

Non-Hodgkin Lymphoma(1);Colorectal Cancer(1);Uterine Sarcoma(1);Ovarian Cancer(1);Small Bowel Cancer(1);“Skin Cancer, Non-Melanoma”(1)

CDKN2A

p.V106 V

c.318G > A

Melanoma(1);Non-Small Cell Lung Cancer(2);Breast Cancer(1);Colorectal Cancer(1);Gastrointestinal Stromal Tumor(1)

ERBB4

p.E452K

c.1354G > A

Skin Cancer, Non-Melanoma(2);Melanoma(4)

ERCC3

p.R742W

c.2224C > T

Glioma(1);Sex Cord Stromal Tumor(1);Renal Cell Carcinoma(1);Non-Small Cell Lung Cancer(1);Leukemia(1);Colorectal Cancer(1)

FBXW7

p.R441W

c.1321C > T

Colorectal Cancer(3);Endometrial Cancer(1);Renal Cell Carcinoma(1);Esophagogastric Cancer(1)

IGF1R

p.R1246C

c.3736C > T

CNS Cancer(1);Endometrial Cancer(2);“Skin Cancer, Non-Melanoma”(1);Breast Cancer(1);Glioma(1)

IKZF1

p.E304K

c.910G > A

Melanoma(6)

KMT2D

p.K4832 N

c.14496G > T

Ovarian Cancer(1);Breast Cancer(1);Colorectal Cancer(2);Head and Neck Cancer(1);Thymic Tumor(1)

MET

p.D1028H

c.3082G > C

Non-Small Cell Lung Cancer(6)

MET

p.D1028Y

c.3082G > T

Non-Small Cell Lung Cancer(6)

MYC

p.S161 L

c.482C > T

Ovarian Cancer(1);Endometrial Cancer(2);Colorectal Cancer(2);Cervical Cancer(1)

PDCD1

p.T36 fs

c.104delC

Endometrial Cancer(2);Non-Small Cell Lung Cancer(1);Glioma(1);Colorectal Cancer(2)

PDCD1LG2

p.P81S

c.241C > T

Colorectal Cancer(1);Head and Neck Cancer(1);Appendiceal Cancer(1);Mesothelioma(1);Leukemia(1);Pancreatic Cancer(1)

PIK3C2B

p.G1435R

c.4303G > C

Head and Neck Cancer(1);Ovarian Cancer(1);Sellar Tumor(1);Appendiceal Cancer(1);Non-Small Cell Lung Cancer(1);Breast Cancer(1)

PMS2

p.K651R

c.1952A > G

Bladder Cancer(2);Uterine Sarcoma(1);Endometrial Cancer(1);Colorectal Cancer(2)

RAF1

p.S259F

c.776C > T

Small Bowel Cancer(1);Bladder Cancer(1);Non-Small Cell Lung Cancer(1);Melanoma(3)

ROS1

p.G1915R

c.5743G > A

Melanoma(1);“Skin Cancer, Non-Melanoma”(1);Non-Small Cell Lung Cancer(1);Breast Cancer(2);Cancer of Unknown Primary(1)

SMAD4

p.D351N

c.1051G > A

Appendiceal Cancer(1);Bladder Cancer(1);Hepatobiliary Cancer(1);Breast Cancer(1);Colorectal Cancer(2)

SMAD4

p.R361S

c.1081C > A

Pancreatic Cancer(1);Hepatobiliary Cancer(1);Colorectal Cancer(4)

SMAD4

p.G419 W

c.1255G > T

Colorectal Cancer(6)