SCN5A Variant V405L

Summary of observed carriers, functional annotations, and structural context for SCN5A V405L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

42%

2/10 effective observations

Estimated BrS1 penetrance

14%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V405L has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 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 0.681 12 57

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 12 2 1 – –

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 V405L.
Neighbour residue Distance (Å) Observed variants
403 8
414 15 M414V,
896 14 C896S, C896S,
404 5 L404V, L404Q,
895 14 L895F,
1765 11
396 12 V396L, V396A,
247 14 V247L, V247L,
1653 15
254 11
372 13
1771 9 I1771T,
401 5 S401P,
926 12
1764 11 c.5290delG, V1764F,
371 9 Q371E,
250 11
409 7 L409V, L409P,
928 7 L928P,
925 14 I925F,
1650 12 L1650F,
260 13
366 11
365 14
933 13
258 14 V258A,
246 14
935 11 L935P,
412 11 V412D,
897 12 G897R, G897R, G897E,
924 11 V924I,
1470 15
927 9 N927S, N927K, N927K,
1466 13 c.4396_4397insG,
369 7 M369K,
1767 10 Y1767C,
1769 12
402 7 F402L, F402L, F402L,
1649 15 A1649V,
1768 8 I1768V,
256 12
399 12
397 10 I397V, I397F, I397T,
405 0
1657 14
261 13
920 14
1709 13 p.T1709del, T1709R, T1709M,
930 13 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1772 10 L1772V,
251 15
410 9 A410V,
1770 13 I1770V,
929 11
413 13 A413T, A413E,
408 5
374 15 W374G,
253 11
407 7
367 14 R367C, R367H, R367L,
936 14
1760 14
1775 13 F1775V, p.F1775LfsX15
370 8 T370M,
923 11
406 4 N406S, N406K, N406K,
368 12
899 14
1710 15 S1710L,
411 11 V411M,
932 8
398 12
1647 15
257 10
400 8 G400R, G400R, G400E, G400A,
931 11
1646 13
1463 13 N1463Y,