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. 2010 Jun 7;5(6):e10985. doi: 10.1371/journal.pone.0010985

Table 3. Correlation between SCN5A mutations, the patients' phenotypes, and electrophysiological properties of hNav1.5 mutant channels associated with SSS and other SCN5A channelopathies.

SCN5A genotype SSS phenotype F/P/I Age of onset of symptoms (years) Other reported phenotypes Surface expression Peak current density Steady-state availability Steady-state activation Current decay Recovery References
P1298L 1/3/n.s. 2–7 none reported  =  ↓a) reduced  =  faster  =  [16], [29]
G1408R BrS, CCD  =  no current
DelF1617 1/1/n.s. 5 BrS, LQT3  =   =  reduced negative shift faster c) faster [16], [33], [41]
R1632H AV block  =   =  reduced  =  faster c) slower
T220I 1/1/n.s. 9 DCM  =  ↓ reduced  =  faster slower b) [16], [31], [32]
R1623X BrSd), AV block ↓ no current
T187I 1/2/positive 33 BrS ↓ no current [31]
R878C 1/2/positive 8, 20 ST elevation  =  no current [30]
W1421X 1/2/n.s. 2–30 CCD, AV block ↓ no current [42]
K1578fs/52 1/1/n.s. 68 BrS, AV block ↓ no current [31]
E161K 2/6/positive 47 BrS, CCD ↓ ↓  =  positive shift slower  =  [20]
L212P 1/1e)/negative 3 none reported  =   =  reduced negative shift faster slower a) [34]
D1275N 2f)/17/positive 12–34 DCM, CCD, AF, AV block ↓ ↓ reduced a) positive shift  =  faster [26], [32]

Loss-of-function features in heterologously expressed hNav1.5 mutant channels, compared to wild-type hNav1.5, are highlighted (bold). F - number of affected families, P - number of patients carrying the mutation(s), I - inheritability for SSS, n.s. - not shown.

a)

Observed only in Xenopus oocytes.

b)

Observed only in HEK293 cells.

c)

Reduced voltage dependency of channel inactivation, resulting in faster current decay at less depolarized potentials and slower decay at more depolarized potentials (Fig. 2F).

d)

R1623X alone caused BrS plus SSS in another unrelated patient [31].

e)

Atrial standstill in this patient was related to a Cx40 polymorphism [34].

f)

In other studies, D1275N was related to atrial flutter, cardiac conduction defects, and bradycardia [27], and in combination with a rare Cx40 polymorphism in another family, with atrial standstill [17].