SCN5A Variant W879R

Summary of observed carriers, functional annotations, and structural context for SCN5A W879R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/12 effective observations

Estimated BrS1 penetrance

68%

8/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

W879R has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 6 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 (%)
-13.52 0.998 -2.56 0.903 93 0

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
29325976 2018 1 0 1 0
29759671 2018 1 0 1 0
Literature, cohort, and gnomAD – 2 0 0 2 –
Variant features alone – 15 9 0 6 – –

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)
32533946 2020 HEK 0
29325976 2018
29759671 2018

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 W879R.
Neighbour residue Distance (Å) Observed variants
891 11 I891T, I891N
880 7
888 11
890 7 I890T,
901 8 S901L, E901K,
919 14
862 14
896 13 C896S, C896S,
895 14 L895F,
1430 12 D1430N,
1426 8
894 11 I894M,
1447 11
1444 10 L1444I,
1440 9 W1440X,
1429 10
1450 13
904 14 W904X,
887 9
1451 14 V1451L, V1451D,
886 6 H886P, H886Q, H886Q,
871 15
897 14 G897E, G897R, G897R,
909 15
1423 9 D1423H,
854 14 c.2559delT,
876 10
1422 6 M1422R,
857 14 G857D,
1418 14
902 8
882 12
892 11 F892I,
373 15
881 10
898 10
893 7 R893H, R893C,
889 7
1420 12 G1420V, G1420R, G1420P, G1420D,
900 13
858 14 M858L, M858L,
1425 8
865 11
1427 12 A1427S, A1427E,
1424 12 I1424V,
1448 15 I1448T, I1448L,
884 13
906 12
874 15 G874D,
878 4 R878L, R878C, R878H,
1421 10
885 11
1443 15 N1443S,
903 14 p.M903CfsX29,
1441 12 E1441Q,
877 6
879 0 W879R, W879R,
883 11
905 10
899 14
875 13
1415 14
1428 12 A1428V, A1428S,
908 15
861 15 c.2582_2583delTT, p.F861WfsX90,
1419 15 K1419E,