SCN5A Variant C982R

Summary of observed carriers, functional annotations, and structural context for SCN5A C982R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

1/39 effective observations

Estimated BrS1 penetrance

2%

0/39 effective observations

Total carriers

29

0 BrS1 · 1 LQT3 · 28 unaffected

C982R is present in 28 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 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 (%)
-0.54 0.979 -0.14 0.45 1 17

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
16712702 2006 1 0 0 1 Sudden adult death syndrome
20102864 2010 1 0 0 1 SUD
27000522 2017 2 0 0 2 SUDS
26746457 2016 2 1 0 1 BBB, AV node disease
Literature, cohort, and gnomAD – 29 28 1 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)
16712702 2006
20102864 2010
27000522 2017
26746457 2016

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 C982R.
Neighbour residue Distance (Å) Observed variants
967 15 Q967R,
968 14
969 14 G969C, G969S,
970 13
971 13 R971H, R971C,
972 12 c.2914_2923delTTTGTCAAGC,
973 11
974 11 K974D,
975 10 R975W, R975Q,
976 9
977 8
978 8
979 7 D979H,
980 5
981 4 C981F,
982 0 C982R,
983 4 G983D,
984 5
985 7
986 8 R986L, R986W, R986Q,
987 8
988 9 R988W, R988Q,
989 10
990 11
991 11 K991E, K991T,
992 12
993 13 A993T, A993S,
994 13 A994V, A994T,
995 14 L995F,
996 14 A996T,
997 15 A997S, A997T, A997D