Table 3 SUMF1 mutations identified in MSD patients

1

c.[463 T > C] + [1029G > T]

3 and 9

p.[S155P] + [R343S]

p.S155P: loss of three hydrogen bonds and steric clash with Ala186 [12]. p.R343S: direct interaction with both sulfhydryl groups of the catalytic Cys336/Cys341 pair. Might affect substrate binding and reactivity.

2

c.[836C > T] + [836C > T]

6

p.[A279V] + [A279V]

Steric clash with Phe275 and Ala283 [12].

3

c.[836C > T] + [836C > T]

6

p.[A279V] + [A279V]

Idem

4

c.[836C > T] + [836C > T]

6

p.[A279V] + [A279V]

Idem

5

c.[893C > A] + [519 + 4A > G]

7 and 3

p.[A298E] + [A149_A173del, A175del]

p.A298E: neither affects FGE fold nor binding to the Ca²⁺ ion at site 2.

6

c.[788G > T] + [788G > T]

6

p.[G263V] + [G263V]

Steric clash with Thr263 and Thr270 [12].

7

c.[520_954dup (+) 520_954dup]

4 to 7

p.[V174_P318dup] + [V174_P318dup]

8

c.[706C > T] + [1045C > T]

5 and 9

p.[R236X] + [R349W]

p.R349W: loss of five interactions [12]. Should affect protein fold in the vicinity of the active site.

9

c.[132_133insG] + [1045C > T]

1 and 9

p.[V45fsX75] + [R349W]

idem

10

c.[776A > G;1018 T > C] + [725 + 1G > C]

6, 9 and 5

p.[N259S; Y340H] + [P202_R242del]

p.N259S precludes binding to Ca²⁺ ion at site 1. p.Y340H should not induce major structural changes.