SCN5A Variant R988Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R988Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/24 effective observations

Estimated BrS1 penetrance

9%

2/24 effective observations

Total carriers

14

1 BrS1 · 0 LQT3 · 13 unaffected

R988Q is present in 13 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 (%)
-0.79 0.001 0.09 0.371 9 3

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
28341781 2017 1 0 1 0
Literature, cohort, and gnomAD – 14 13 0 1 –
Variant features alone – 15 14 0 1 – –

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)
28341781 2017

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 R988Q.
Neighbour residue Distance (Å) Observed variants
973 15
974 14 K974D,
975 14 R975W, R975Q,
976 13
977 13
978 12
979 11 D979H,
980 11
981 10 C981F,
982 9 C982R,
983 8 G983D,
984 8
985 7
986 5 R986L, R986W, R986Q,
987 4
988 0 R988W, R988Q,
989 4
990 5
991 7 K991E, K991T,
992 8
993 8 A993T, A993S,
994 9 A994V, A994T,
995 10 L995F,
996 11 A996T,
997 11 A997S, A997T, A997D
998 12
999 13 G999D,
1000 13 Q1000X, p.Gln1000del, Q1000L,
1001 14
1002 14 c.3005-3012delCCAGCTGG, P1002S,
1003 15