SCN5A Variant R282C

Summary of observed carriers, functional annotations, and structural context for SCN5A R282C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/13 effective observations

Estimated BrS1 penetrance

49%

6/13 effective observations

Total carriers

3

2 BrS1 · 0 LQT3 · 1 unaffected

R282C has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
-4.42 1 -2.84 0.914 54 1

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
26921764 2016 1 0 1 0
26746457 2016 1 0 0 0
20129283 2010 1 0 1 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 3 1 0 2 –
Variant features alone – 15 11 0 4 – –

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)
26921764 2016
26746457 2016
20129283 2010
30059973 2018
32533946 2020 HEK 1

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 R282C.
Neighbour residue Distance (Å) Observed variants
287 12
341 12 C341Y,
342 11
326 13
335 11 C335S, C335R, C335S,
339 5
319 8 G319S, G319R, G319C,
317 14 K317E, K317M, K317N, K317N,
284 6
336 9 P336L,
282 0 R282C, R282H,
279 12
324 14
321 11 S321Y,
344 14 A344S
340 9 R340W, R340Q,
285 6 T285K,
338 6
322 14
280 8 C280Y,
318 12
281 6 V281M,
323 11
283 6
337 10
286 8 A286S, A286V,
320 9 T320N,