SCN5A Variant V924I

Summary of observed carriers, functional annotations, and structural context for SCN5A V924I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/43 effective observations

Estimated BrS1 penetrance

2%

0/43 effective observations

Total carriers

33

0 BrS1 · 0 LQT3 · 33 unaffected

V924I is present in 31 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 (%)
-0.82 0.027 3.48 0.525 8 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
20129283 2010 2 0 0 0
Literature, cohort, and gnomAD – 33 33 0 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)
20129283 2010
32533946 2020 HEK 95 5.2 4.7

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 V924I.
Neighbour residue Distance (Å) Observed variants
891 12 I891N, I891T,
919 11
363 15
896 13 C896S, C896S,
404 12 L404V, L404Q,
895 10 L895F,
249 14 K249X,
894 10 I894M,
247 9 V247L, V247L,
254 9
372 14
401 14 S401P,
926 6
371 15 Q371E,
250 9
409 12 L409V, L409P,
928 5 L928P,
925 4 I925F,
366 10
933 12
258 14 V258A,
246 10
412 12 V412D,
897 11 G897R, G897R, G897E,
924 0 V924I,
927 7 N927S, N927K, N927K,
852 15
245 15 Q245K,
369 12 M369K,
845 15 c.2533delG,
244 13
849 11
898 15
921 6
922 6 V922I,
405 11
362 15
248 13
261 14
920 7
930 9 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T
255 15
918 10
917 11 L917V, L917R,
251 12
916 12
410 14 A410V,
242 14 A242D,
929 6
408 9
253 12
407 13
846 13 L846R,
903 14 p.M903CfsX29,
853 11
370 11 T370M,
923 5
406 14 N406S, N406K, N406K,
899 11
850 13 V850M, c.2549_2550insTG,
411 13 V411M,
243 11
932 10
257 12
931 10