Table 2.

TP53 variants, pathogenicity and types of cancers

TP53 variant	Pathogenicity	Subjects (n)	Individual	Sex (male/female)	Type of test: predictive (P)/diagnostic (D)	Types of cancer (age at diagnosis of cancer or at last f/u if no cancer diagnosed, years)	Cause of death/alive at last f/u
c.1010G>A (R337H)	Pathogenic/likely pathogenic	3	1	F	D	•Leiomyosarcoma (33)	Metastatic leiomyosarcoma
			2	M	D	•Prostate cancer (55) •Renal cell carcinoma (65)	Metastatic prostate cancer
			3	F	P	•No cancers diagnosed at last f/u (48)	Alive at last f/u
c.1024C>T	Pathogenic	4	1	F	D	•Malignant phyllodes of the breast (17) •Liposarcoma of the vulva (19) •Thyroid carcinoma (25)	Alive at last f/u
			2	F	P	•Granulosa cell tumour of the ovary (29) •Basal cell carcinoma skin (33)	Alive at last f/u
			3	F	D	•Breast cancer (27, 37)	Metastatic breast cancer
			4	F	P	•No cancers diagnosed at last f/u (43)	Alive at last f/u
c.1031T>C	Pathogenic	1	1	M	D	•Colorectal adenocarcinoma (33) •Leiomyosarcoma bilateral thighs (36, 52) •Glioblastoma (57)	Glioblastoma
c.151G>T	Likely pathogenic	1	1	F	D	•Ovarian germ cell tumour (21) •Embryonal carcinoma of vagina (24)	Metastatic carcinoma
c.196C>T	Pathogenic	1	1	F	P	•Glioblastoma (45) •Renal carcinoma (45) •Leiomyosarcoma (45)	Glioblastoma NB: all three cancers were diagnosed in the same year—renal and uterine cancer detected on a one-off WB-MRI and the glioblastoma diagnosed following emergency admission with neurological symptoms
c.273G>A	Pathogenic	1	1	F	D	•Hepatocellular carcinoma (2) •Leiomyosarcoma (24, 41) •Breast cancer (29) •Basal cell carcinoma skin (40)	Alive at last f/u
c.314_315delinsAT	Pathogenic	1	1	M	D	•Prostate cancer (61)	Metastatic prostate cancer
c.375G>A	Pathogenic	1	1	F	P	•No cancers diagnosed at last f/u (49)	Alive at last f/u
c.377A>G	Likely pathogenic	1	1	M	P	•Sarcoma (31)	Metastatic sarcoma
c.422G>A	Pathogenic/likely pathogenic	1	1	F	D	•B-cell acute lymphoblastic leukaemia treated with whole body irradiation (15) •Leiomyosarcoma (29, 32) •Melanoma (31) •Breast cancer (32)	Patient lost to f/u following her last cancer diagnosis
c.455C>T	Pathogenic	7	1	M	D	•Chondrosarcoma (14)	Alive at last f/u
			2	F	D	•Diffuse large B-cell lymphoma (52)	Relapse lymphoma in CNS
			3	F	P	•Astrocytoma (33)	Alive at last f/u
			4	M	D	•Myxofibrosarcoma (51) •Bladder carcinoma (55)	Alive at last f/u
			5	M	P	•No cancers diagnosed at last f/u (51)	Alive at last f/u
			6	F	P	•No cancers diagnosed at last f/u (60)	Alive at last f/u
			7	F	P	•No cancers diagnosed at last f/u (62)	Alive at last f/u
c.473G>A	Pathogenic/likely pathogenic	4	1	F	D	•Breast cancer (56) •Leiomyosarcoma (56)	Encephalopathy probably sarcoma related
			2	M	D	•Chondrosarcoma (22) •Rectal adenocarcinoma (43)	Alive at last f/u
			3	F	P	•No cancers diagnosed at last f/u (42)	Alive at last f/u
			4	F	P	•No cancers diagnosed at last f/u (56)	Alive at last f/u
c.524G>A	Pathogenic	2	1	F	D	•Breast cancer (31) •Leiomyosarcoma (36) •Lung adenocarcinoma (38)	Metastatic leiomyosarcoma
			2	M	D	•Sarcoma MPNST (32) •Glioblastoma (35)	Glioblastoma
c.589G>A	Likely pathogenic	2	1	F	P	•Breast cancer HR+; HER2− (36)	Metastatic breast cancer
			2	F	P	•Breast cancer ER+; HER2− (46)	Alive at last f/u
c.638_639delinsAG	Pathogenic	1	1	F	P	•No cancers diagnosed at last f/u (47)	Alive at last f/u
c.638G>A	Pathogenic	3	1	F	D	•Breast cancer HR+; HER2− (38)	Lost to f/u
			2	F	D	•Leiomyosarcoma (31) •Ductal carcinoma in situ breast (46)	Metastatic leiomyosarcoma (LFS diagnosed post-mortem)
			3	F	P	•One person with no cancer diagnosed at last f/u (42)	Alive at last f/u
c.659A>G	Likely pathogenic	2	1	F	D	•Breast cancer—Paget’s disease (28) •Sarcoma of ethmoid (34) •Radiation-induced squamous cell skin carcinoma (45)	Lost to f/u
			2	F	D	•Adrenal carcinoma (4) •Breast cancer HR+, HER2+ (26)	Metastatic breast cancer
c.694A>T	Likely pathogenic	2	1	F	P	•Chronic lymphocytic leukaemia (55)	Alive at last f/u
			2	F	P	•Lung adenocarcinoma (49)	Metastatic lung cancer
c.715A>G	Likely pathogenic	1	1	F	D	•Ewings sarcoma (11) •Astrocytoma (25)	Astrocytoma
c.733G>A	Pathogenic	1	1	F	D	•Breast cancer bilateral (32, 37) •Gastric carcinoma (50)	Alive at last f/u
c.745_726del9	Likely pathogenic	1	1	F	D	•Myxofibrosarcoma (39)	Metastatic myxofibrosarcoma
c.766A>G	Likely pathogenic in 2016, then downgraded to variant of uncertain significance in 2022	2	1	F	P	•Bilateral breast cancer (72)	Alive at last f/u
			2	F	D	•Bilateral breast cancer (34) •Pancreatic adenocarcinoma (59)	Metastatic pancreatic cancer
c.818G>A	Pathogenic	6	1	F	P	•Breast cancer (31)	Alive at last f/u
			2	F	D	•Breast cancer (34) •Acute myeloid leukaemia (43)	Acute leukaemia
			3	F	D	•Ductal carcinoma in situ right (44) •Bilateral breast cancer (48)	Alive at last f/u
			4	F	D	•Malignant phyllodes of the breast (18) •Contralateral ductal carcinoma in situ (22) •Endometrioid ovarian cancer (26)	Alive at last f/u
			5	F	P	•No cancers diagnosed at last f/u (22)	Alive at last f/u
			6	M	P	•No cancers diagnosed at last f/u (23)	Alive at last f/u
c.824G>A	Pathogenic/likely pathogenic	1	1	F	D	•Bilateral breast cancer (45, 48) •Liposarcoma (47)	Metastatic liposarcoma
c.844C>T	Pathogenic/likely pathogenic	2	1	F	D	•Rhabdomyosarcoma (1) •Breast cancer (25) •Radiation-induced osteosarcoma (26)	Metastatic breast cancer
			2	F	D	•Embryonal rhabdomyosarcoma (6 months) •Bilateral ductal carcinoma in situ (25) •Malignant PEComa (sarcoma) (25) •Osteosarcoma (27)	Metastatic osteosarcoma
Exon 1 deletion	Likely pathogenic	2	1	M	D	•Dermal sarcoma shoulder (29) •Retroperitoneal leiomyosarcoma (42)	Metastatic leiomyosarcoma
			2	F	D	•Breast cancer (50) •Lung adenocarcinoma (bilateral) (51, 69) •Pelvic leiomyosarcoma (64)	Alive at last f/u
Exon 1-5 deletion	Pathogenic	1	1	F	P	•Basal cell carcinoma (53)	Alive at last f/u
Exon 1-11 deletion	Likely pathogenic	1	1	M	P	•No cancers diagnosed at last f/u (43)	Lost to f/u
Whole gene deletion	Likely pathogenic	1	1	F	D	•Breast cancer (53)	Metastatic breast cancer (LFS diagnosed post-mortem)

Of note, the same kind of cancer can be diagnosed in two separate individuals carrying the same TP53 variant, and commas separate their ages. If there is only one person with a specific variant, each cancer diagnosis is listed separately, with the respective age at each diagnosis. For example, the person carrier of the c.1031T>C variant was diagnosed with four different cancers and had a leiomyosarcoma on each thigh diagnosed at 36 and 52 years old; the second leiomyosarcoma was considered to be a separate occurrence from the first leiomyosarcoma. Recurrences are not shown in this table, due to the short interval of follow-up, but the cause of death is shown in the last column.

CNS, central nervous system; D, diagnostic; ER, estrogen receptor; F, female; f/u, follow-up; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; LFS, Li Fraumeni syndrome; M, male; MPNST, malignant peripheral nerve sheath tumour; P, predictive; PEComa, perivascular epithelioid cell tumor; WB-MRI, whole-body magnetic resonance imaging.