SCN5A Variant R971C

Summary of observed carriers, functional annotations, and structural context for SCN5A R971C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

1/14 effective observations

Estimated BrS1 penetrance

12%

1/14 effective observations

Total carriers

4

0 BrS1 · 1 LQT3 · 3 unaffected

R971C is present in 3 alleles in gnomAD. This residue resides in a Mild_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 (%)
-2.11 0.99 0.15 0.741 12 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
15840476 2005 1 1 0 0
27566755 2016 1 1 0 0
Literature, cohort, and gnomAD – 4 3 1 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)
15840476 2005
27566755 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 R971C.
Neighbour residue Distance (Å) Observed variants
956 15 M956I, M956I, M956I, M956T,
957 14
958 14
959 13 L959P,
960 13 Q960K,
961 12
962 11
963 11
964 10 A964G,
965 9 R965C, R965L, R965H,
966 8
967 8 Q967R,
968 7
969 5 G969C, G969S,
970 4
971 0 R971C, R971H,
972 4 c.2914_2923delTTTGTCAAGC,
973 5
974 7 K974D,
975 8 R975Q, R975W,
976 8
977 9
978 10
979 11 D979H,
980 11
981 12 C981F,
982 13 C982R,
983 13 G983D,
984 14
985 14
986 15 R986L, R986Q, R986W,