SCN5A Variant Q1000L

Summary of observed carriers, functional annotations, and structural context for SCN5A Q1000L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

9%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

Q1000L is present in 1 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 1 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 (%)
-1.91 0.183 -0.19 0.424 4 2

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 – 1 1 0 0 –
Variant features alone – 15 14 0 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 Q1000L.
Neighbour residue Distance (Å) Observed variants
985 15
986 14 R986L, R986W, R986Q,
987 14
988 13 R988W, R988Q,
989 13
990 12
991 11 K991E, K991T,
992 11
993 10 A993T, A993S,
994 9 A994V, A994T,
995 8 L995F,
996 8 A996T,
997 7 A997S, A997T, A997D
998 5
999 4 G999D,
1000 0 Q1000X, p.Gln1000del, Q1000L,
1001 4
1002 5 c.3005-3012delCCAGCTGG, P1002S,
1003 7
1004 8 C1004R,
1005 8 I1005V, I1005T,
1006 9 A1006S,
1007 10 T1007I, T1007N,
1008 11 P1008S,
1009 11
1010 12
1011 13 P1011S, P1011L,
1012 13
1013 14
1014 14 P1014S,
1015 15 E1015K, p.G1015DfsX14,