SCN5A Variant H886Q

Summary of observed carriers, functional annotations, and structural context for SCN5A H886Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/17 effective observations

Estimated BrS1 penetrance

44%

7/17 effective observations

Total carriers

7

4 BrS1 · 0 LQT3 · 3 unaffected

H886Q has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-7.62 0.993 2.19 0.766 53 0

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
29709101 2018 7 0 4 0
Literature, cohort, and gnomAD – 7 3 0 4 –
Variant features alone – 15 12 0 3 – –

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)
29709101 2018

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 H886Q.
Neighbour residue Distance (Å) Observed variants
891 10 I891N, I891T,
880 5
888 8
856 14 V856L, V856L,
890 7 I890T,
901 14 S901L, E901K,
919 15
862 11
859 15
1430 13 D1430N,
1426 11
1445 12 Y1445H,
894 13 I894M,
1447 9
1444 7 L1444I,
153 14
1440 9 W1440X,
149 13
1429 11
1442 13 Y1442C, Y1442N,
1450 14
887 5
1451 14 V1451D, V1451L,
864 15
886 0 H886Q, H886Q, H886P,
851 14 c.2552_2553dupGT, F851L, F851L, p.F851CfsX19, F851L, c.2550_2551dupGT,
1423 15 D1423H,
854 10 c.2559delT,
876 10
1422 12 M1422R,
857 11 G857D,
902 12
882 8
892 11 F892I,
881 7
893 11 R893C, R893H,
889 6
858 10 M858L, M858L,
855 12
1425 11
865 10
1427 14 A1427S, A1427E,
1446 13
1448 13 I1448L, I1448T,
884 8
906 14
866 14 S866P, S866L,
878 9 R878H, R878C, R878L,
1421 14
885 6
1443 13 N1443S,
1441 9 E1441Q,
152 11 D152N,
853 15
877 9
151 15
879 6 W879R, W879R,
883 5
905 13
875 14
1428 14 A1428S, A1428V,
850 14 c.2549_2550insTG, V850M
861 13 c.2582_2583delTT, p.F861WfsX90,