Table 1 Sample list and variants.

From: Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood

Sample

Patient sex

Patient age (years)

Batch

Used for

Predicted pathogenicity

Sample type

TET3 variant(s)

1a

Female

3

1

Signature discovery

Pathogenic

TET3 (BA)

c.3215T>G (p.Phe1072Cys)c; c.3226G>A (p.Ala1076Thr)c

2a

Male

21

1

Signature discovery

Pathogenic

TET3 (BA)

c.2722G>T (p.Val908Leu); c.2722G>T (p.Val908Leu)c

3a

Female

27

1

Signature discovery

Pathogenic

TET3 (BA)

c.2722G>T (p.Val908Leu); c.2722G>T (p.Val908Leu)c

4a

Male

5

1

Signature discovery

Pathogenic

TET3 (MA)

c.4977_4983del (p.His1660Profs*52)

5a

Male

57

1

Signature discovery

Pathogenic

TET3 (MA)

c.4977_4983del (p.His1660Profs*52)

6a

Female

11

1

Signature discovery

Pathogenic

TET3 (MAb)

c.3265G>A (p.Val1089Met)c; c.2254C>T (p.Arg752Cys)c

7

Female

10

1

Signature validation

NA

Family member controld

Familial variant absent by Sanger sequencing

8

Male

23

1

Signature validation

NA

Family member controle

Familial variant absent by Sanger sequencing

9

Female

44

1

Signature validation

NA

Family member controlf

Familial variant absent by exome sequencing

10

Female

10

1

Signature validation

NA

Family member controlg

Familial variants absent by Sanger, exome sequencing

11

Male

50

1

Signature validation

Benign

TET3 (MA)

c.2254C>T (p.Arg752Cys)c

12a

Male

6

2

Signature validation

Pathogenic

TET3 (MA)

c.5083C>T (p.Gln1695*)

13a

Male

5

2

Signature validation

Pathogenic

TET3 (MA)

c.3100C>T (p.Arg1034*)

14a

Female

46

1

Signature validation

Pathogenic

TET3 (MA)

c.3265G>A (p.Val1089Met)c

15a

Male

64

1

Signature validation

Pathogenic

TET3 (MA)

c.2722G>T (p.Val908Leu)c

16a

Female

28

1

Signature validation

Pathogenic

TET3 (MA)

c.3226G>A (p.Ala1076Thr)c

17

Female

2

2

Testing

Unknown

TET3 VUS (BA)

c.1483C>T (p.Pro495Ser); c.3883G>A (p.Val1295Ile)

18

Female

11

1

Testing

Unknown

TET3 VUS (BA)

c.4513G>A (p.Gly1505Arg); c. 5237G>C (p.Trp1746Ser)

19

Female

27

2

Testing

Unknown

TET3 VUS (MA)

c.1483C>T (p.Pro495Ser)

20

Male

46

2

Testing

Unknown

TET3 VUS (MA)

c.3883G>A (p.Val1295Ile)

21a

Male

21

2

Testing

Unknown

TET3 VUS (MA)

c.2732G>A (p.Arg911Gln)

22a

Male

9

4

Testing

Unknown

TET3 VUS (MA)

c.5048G>A p.(Arg1683His)

23

Female

42

1

Testing

Unknown

TET3 VUS (MA)

c.4513G>A (p.Gly1505Arg)

24

Male

47

1

Testing

Unknown

TET3 VUS (MA)

c.5237G>C (p.Trp1746Ser)

25a

Female

54

1

Testing

Unknown

TET3 VUS (MA)

c.2036dupC (p.Thr680Tyrfs*26)h

26a

Male

6

1

Testing

Unknown

TET3 VUS (MA)

c.2036dupC (p.Thr680Tyrfs*26)h

27a

Male

1

3

Testing

Unknown

Episign screen

c.738C>A (p.Cys246*)

  1. BA bi-allelic, MA mono-allelic, NA not applicable.
  2. aTET3-deficient pathogenic samples used to identify the final DNA methylation episignature.
  3. bConsidered mono-allelic because only the c.3265G>A (p.Val1089Met) variant reduced catalytic activity in vitro, suggesting pathogenicity; c.2254C>T (p.Arg752Cys) did not reduce catalytic activity in vitro (ref. 8), suggesting non-pathogenicity.
  4. cVariants previously tested in our in vitro assay (ref. 8).
  5. dUnaffected daughter of Sample 5 and sister of Sample 4.
  6. eUnaffected son of 25 and brother of 26.
  7. fUnaffected mother of Sample 4.
  8. gUnaffected sister of Sample 6 and daughter of Samples 11 and 14.
  9. hPreviously considered VUS because mother was not thought to be affected; upon further evaluation, she was noted to be affected (see text for details).
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