SCN5A Variant L928P

Summary of observed carriers, functional annotations, and structural context for SCN5A L928P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

54%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

L928P 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 (%)
-6.39 0.484 -5.98 0.966 66 7

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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
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)
20129283 2010
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 L928P.
Neighbour residue Distance (Å) Observed variants
403 15
414 15 M414V,
891 14 I891N, I891T,
919 14
896 11 C896S, C896S,
404 10 L404V, L404Q,
895 10 L895F,
842 14
249 14 K249X,
894 11 I894M,
247 10 V247L, V247L,
254 10
372 13
1771 15 I1771T,
401 11 S401P,
926 6
371 12 Q371E,
250 9
409 8 L409V, L409P,
928 0 L928P,
925 7 I925F,
366 11
934 13
933 10
258 15 V258A,
246 10
935 11 L935P,
412 9 V412D,
897 10 G897R, G897R, G897E,
924 5 V924I,
927 4 N927S, N927K, N927K,
245 15 Q245K,
369 10 M369K,
244 15
402 14 F402L, F402L, F402L,
415 14 A415T,
1768 13 I1768V,
849 13
898 14
256 15
921 10
922 9 V922I,
405 7
248 15
261 15
920 10
930 8 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 13 c.4376_4379delTCTT,
1772 14 L1772V
918 14
251 13
410 11 A410V,
242 13 A242D,
929 5
416 15 Y416C,
413 12 A413T, A413E,
408 6
253 11
407 10
846 13 L846R,
367 15 R367C, R367H, R367L,
936 13
853 14
370 9 T370M,
923 6
406 10 N406S, N406K, N406K,
368 15
899 12
850 14 V850M, c.2549_2550insTG,
411 10 V411M,
243 11
932 6
257 12
400 14 G400R, G400R, G400E, G400A,
931 7
1463 14 N1463Y,