SCN5A Variant C981F

Summary of observed carriers, functional annotations, and structural context for SCN5A C981F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

54%

3/11 effective observations

Estimated BrS1 penetrance

8%

0/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

C981F has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-1.08 0.994 0 0.504 1 59

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 13 2 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)
27337590 2016 HEK -3.9 -9.4
19716085 2009

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 C981F.
Neighbour residue Distance (Å) Observed variants
966 15
967 14 Q967R,
968 14
969 13 G969C, G969S,
970 13
971 12 R971C, R971H,
972 11 c.2914_2923delTTTGTCAAGC,
973 11
974 10 K974D,
975 9 R975W, R975Q,
976 8
977 8
978 7
979 5 D979H,
980 4
981 0 C981F,
982 4 C982R,
983 5 G983D,
984 7
985 8
986 8 R986L, R986W, R986Q,
987 9
988 10 R988Q, R988W,
989 11
990 11
991 12 K991E, K991T,
992 13
993 13 A993T, A993S,
994 14 A994V, A994T,
995 14 L995F,
996 15 A996T,