SCN5A Variant V412A

Summary of observed carriers, functional annotations, and structural context for SCN5A V412A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

27%

1/10 effective observations

Estimated BrS1 penetrance

32%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V412A has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
NA NA NA 0.946 43 34

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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 11 1 3 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 V412A.
Neighbour residue Distance (Å) Observed variants
414 6 M414V,
939 11 L939F,
404 13 L404V, L404Q,
937 11
1773 14
842 12
249 9 K249X,
247 9 V247L, V247L,
240 13 V240M,
254 13
1771 13 I1771T,
418 10 E418K,
926 11
250 8
409 5 L409P, L409V,
928 9 L928P,
925 12 I925F,
417 10
934 11
933 6
246 5
935 9 L935P,
1779 13 T1779M,
412 0 V412D,
924 12 V924I,
1470 14
927 11 N927K, N927K, N927S,
1466 14 c.4396_4397insG,
245 9 Q245K,
1776 12
845 15 c.2533delG,
244 11
1769 14
415 6 A415T,
1768 13 I1768V,
940 12 S940N,
405 11
248 12
938 12
241 11
420 12
419 11 Q419X,
930 9 c.2788-6C>T, c.2787+17_2787+18insACACACACACACACACACACACA,
1772 10 L1772V,
239 11 I239V, I239V ,
251 13
410 6 A410V,
1780 15 E1780G,
242 8 A242D,
929 6
416 7 Y416C,
413 4 A413E, A413T,
408 7
253 12
407 9
846 15 L846R,
936 7
238 13
1467 14
1775 10 F1775V, p.F1775LfsX15,
923 15
421 14
406 10 N406K, N406K, N406S,
252 14
411 4 V411M,
243 8
932 6
931 10
1646 14
1463 14 N1463Y,