SCN5A Variant R27H

Summary of observed carriers, functional annotations, and structural context for SCN5A R27H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

1/82 effective observations

Estimated BrS1 penetrance

5%

3/82 effective observations

Total carriers

72

3 BrS1 · 1 LQT3 · 68 unaffected

R27H is present in 66 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 (%)
-3.65 0.994 2.76 0.833 1 3

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
11901046 2002 1 0 1 0
22840528 2012 1 0 1 0
22984773 2013 4 0 2 0
24631775 2014 1 0 0 1 SD
24721456 2014 1 0 1 0
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 72 68 1 3 –
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)
23805106 2013 HEK 82 4 -0.4
11901046 2002
22840528 2012
22984773 2013
24631775 2014
24721456 2014
19716085 2009

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 R27H.
Neighbour residue Distance (Å) Observed variants
12 15
13 14
14 14 R14S, R14C, R14H,
15 13 R15G, R15T, R15M,
16 13 F16L, F16L, F16L,
17 12
18 11 R18W, R18Q,
19 11
20 10 S20F,
21 9 L21V,
22 8 A22V,
23 8 A23S,
24 7
25 5 E25K,
26 4
27 0 R27C, R27H, R27L,
28 4 M28L, M28L, M28T, M28I, M28I, M28I,
29 5 A29E, A29V,
30 7 E30G,
31 8
32 8
33 9
34 10 R34C, R34H,
35 11 G35S,
36 11
37 12 T37A,
38 13
39 13 L39F, L39F
40 14
41 14
42 15