SCN5A Variant R986Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R986Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/20 effective observations

Estimated BrS1 penetrance

7%

1/20 effective observations

Total carriers

10

0 BrS1 · 0 LQT3 · 10 unaffected

R986Q is present in 9 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 (%)
-0.62 0.001 -0.13 0.26 1 21

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
29167113 2018 1 0 0 1 IBS
26129877 2015 1 0 0 1 AF
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 10 10 0 0 –
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)
26129877 2015
20129283 2010
29167113 2018 HEK 3 19.7 14.2

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 R986Q.
Neighbour residue Distance (Å) Observed variants
971 15 R971C, R971H,
972 14 c.2914_2923delTTTGTCAAGC,
973 14
974 13 K974D,
975 13 R975W, R975Q,
976 12
977 11
978 11
979 10 D979H,
980 9
981 8 C981F,
982 8 C982R,
983 7 G983D,
984 5
985 4
986 0 R986L, R986W, R986Q,
987 4
988 5 R988Q, R988W,
989 7
990 8
991 8 K991E, K991T,
992 9
993 10 A993T, A993S,
994 11 A994V, A994T,
995 11 L995F,
996 12 A996T,
997 13 A997T, A997D, A997S,
998 13
999 14 G999D,
1000 14 Q1000X, p.Gln1000del, Q1000L,
1001 15