SCN5A Variant G983D

Summary of observed carriers, functional annotations, and structural context for SCN5A G983D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/18 effective observations

Estimated BrS1 penetrance

3%

0/18 effective observations

Total carriers

8

0 BrS1 · 0 LQT3 · 8 unaffected

G983D is present in 8 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 0 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 (%)
-0.93 0.117 -1.61 0.601 1 10

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
27287068 2016 1 0 0 1 biphasic T-wave morphology
Literature, cohort, and gnomAD 8 8 0 0
Variant features alone 15 15 0 0

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)
27287068 2016 Oocytes 140

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 G983D.
Neighbour residue Distance (Å) Observed variants
968 15
969 14 G969C, G969S,
970 14
971 13 R971H, R971C,
972 13 c.2914_2923delTTTGTCAAGC,
973 12
974 11 K974D,
975 11 R975W, R975Q,
976 10
977 9
978 8
979 8 D979H,
980 7
981 5 C981F,
982 4 C982R,
983 0 G983D,
984 4
985 5
986 7 R986L, R986W, R986Q,
987 8
988 8 R988W, R988Q,
989 9
990 10
991 11 K991E, K991T,
992 11
993 12 A993T, A993S,
994 13 A994V, A994T,
995 13 L995F,
996 14 A996T,
997 14 A997S, A997T, A997D
998 15