SCN5A Variant L409Q

Summary of observed carriers, functional annotations, and structural context for SCN5A L409Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

60%

2/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L409Q has not been reported 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 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 0.974 4 81

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 L409Q.
Neighbour residue Distance (Å) Observed variants
403 12
414 9 M414V,
939 10 L939F,
404 10 L404Q, L404V,
937 12
1773 11
1765 11
842 15
249 12 K249X,
247 13 V247L, V247L,
1653 15
254 14
1771 9 I1771T,
401 12 S401P,
1777 15 V1777M, V1777L, V1777L,
418 14 E418K,
926 12
1764 13 V1764F, c.5290delG,
371 15 Q371E,
250 10
409 0 L409P, L409V,
928 8 L928P,
925 14 I925F,
1650 13 L1650F,
417 12
934 11
933 9
1471 14
246 10
935 7 L935P,
1779 14 T1779M,
412 5 V412D,
924 12 V924I,
1470 10
1464 14 c.4389_4396delCCTCTTTA, L1464P,
927 10 N927S, N927K, N927K,
1466 10 c.4396_4397insG,
245 14 Q245K,
1776 11
369 14 M369K,
1767 12 Y1767C,
1769 10
402 12 F402L, F402L, F402L,
1766 15 M1766L, M1766T, M1766L, M1766V,
415 10 A415T,
1649 14 A1649V,
1768 8 I1768V,
940 13 S940N,
1774 13 N1774D, c.5321_5324dupACTT,
1473 15 F1473S, F1473C,
1468 15 V1468F, V1468A,
405 7
938 12
930 11 c.2788-6C>T, c.2787+17_2787+18insACACACACACACACACACACACA,
1459 14 c.4376_4379delTCTT,
1772 6 L1772V,
410 4 A410V,
242 13 A242D,
1770 12 I1770V,
929 9
416 11 Y416C,
413 6 A413T, A413E,
408 5
253 12
1462 15
407 7
936 8
1467 11
1775 9 F1775V, p.F1775LfsX15,
370 14 T370M,
923 14
1469 13 I1469V,
406 5 N406K, N406K, N406S,
411 7 V411M,
243 13
932 5
257 14
400 14 G400R, G400E, G400A, G400R,
931 10
1646 13
1463 11 N1463Y,