SCN5A Variant R340Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R340Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

2/32 effective observations

Estimated BrS1 penetrance

4%

1/32 effective observations

Total carriers

22

0 BrS1 · 1 LQT3 · 21 unaffected

R340Q is present in 21 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.21 0.984 0.59 0.581 5 43

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
22685113 2012 1 0 0 1 AF
15176425 2004 1 1 0 0
21306642 2011 1 0 0 1 AF
24144883 2014 1 0 0 1 AF
24631775 2014 1 0 0 1 SD
Literature, cohort, and gnomAD – 22 21 1 0 –
Variant features alone – 15 13 1 1 – –

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)
22685113 2012 HEK 86 -6.2 -5.5
15176425 2004
21306642 2011
24144883 2014
24631775 2014

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 R340Q.
Neighbour residue Distance (Å) Observed variants
343 12
328 11
341 6 C341Y,
342 6
326 11
335 9 C335S, C335R, C335S,
327 10
339 7
319 12 G319S, G319R, G319C,
384 14 S384T
325 14 L325R,
317 14 K317E, K317M, K317N, K317N,
284 10
336 10 P336L,
282 9 R282C, R282H,
279 11
321 15 S321Y,
344 12 A344S,
340 0 R340W, R340Q,
338 7
285 14 T285K,
345 14
278 11 H278D, H278R,
334 12 c.999-424_1338+81del,
280 8 C280Y,
281 6 V281M,
318 15
323 14
283 5
337 11
320 12 T320N,