SCN5A Variant R986W
Summary of observed carriers, functional annotations, and structural context for SCN5A R986W. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
25%
1/12 effective observations
Estimated BrS1 penetrance
8%
0/12 effective observations
Total carriers
2
0 BrS1 · 1 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.37 | 0.964 | -3.46 | 0.482 | 1 | 21 |
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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 23631430 | 2013 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 23631430 | 2013 |
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 971 | 15 | R971C, R971H, |
| 972 | 14 | c.2914_2923delTTTGTCAAGC, |
| 973 | 14 | |
| 974 | 13 | K974D, |
| 975 | 13 | R975W, R975Q, |
| 976 | 12 | |
| 977 | 11 | |
| 978 | 11 | |
| 979 | 10 | D979H, |
| 980 | 9 | |
| 981 | 8 | C981F, |
| 982 | 8 | C982R, |
| 983 | 7 | G983D, |
| 984 | 5 | |
| 985 | 4 | |
| 986 | 0 | R986L, R986W, R986Q, |
| 987 | 4 | |
| 988 | 5 | R988Q, R988W, |
| 989 | 7 | |
| 990 | 8 | |
| 991 | 8 | K991E, K991T, |
| 992 | 9 | |
| 993 | 10 | A993T, A993S, |
| 994 | 11 | A994V, A994T, |
| 995 | 11 | L995F, |
| 996 | 12 | A996T, |
| 997 | 13 | A997T, A997D, A997S, |
| 998 | 13 | |
| 999 | 14 | G999D, |
| 1000 | 14 | Q1000X, p.Gln1000del, Q1000L, |
| 1001 | 15 |