SCN5A Variant R34C

Summary of observed carriers, functional annotations, and structural context for SCN5A R34C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

3/2987 effective observations

Estimated BrS1 penetrance

0%

0/2987 effective observations

Total carriers

2977

0 BrS1 · 3 LQT3 · 2974 unaffected

R34C is present in 2928 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-3.7 0.984 -2.76 None 0 2

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
11960580 2001 2 0 0 0
19322600 2009 9 0 0 9 SIDS
21964171 2011 1 0 0 1 SUDS
23714088 2013 2 2 0 0
24687331 2014 1 1 0 0
23571586 2013 1 0 0 1 stillbirth, SUDS
20129283 2010 44 0 0 0
Literature, cohort, and gnomAD – 2977 2974 3 0 –
Variant features alone – 15 15 0 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
15992732 2005 HEK 83 -2 0
11960580 2001
11997281 2002
15851227 2004
15898185 2004
19322600 2009
21964171 2011
23714088 2013
24687331 2014
23571586 2013
15992733 2005
20129283 2010

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near R34C.
Neighbour residue Distance (Å) Observed variants
19 15
20 14 S20F,
21 14 L21V,
22 13 A22V,
23 13 A23S,
24 12
25 11 E25K,
26 11
27 10 R27C, R27H, R27L,
28 9 M28L, M28L, M28T, M28I, M28I, M28I,
29 8 A29E, A29V,
30 8 E30G,
31 7
32 5
33 4
34 0 R34C, R34H,
35 4 G35S,
36 5
37 7 T37A,
38 8
39 8 L39F, L39F,
40 9
41 10
42 11
43 11 R43X, R43Q,
44 12
45 13 G45A,
46 13
47 14
48 14 E48K,
49 15 E49K