SCN5A Variant N1987K
Summary of observed carriers, functional annotations, and structural context for SCN5A N1987K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/13 effective observations
Estimated BrS1 penetrance
2%
0/13 effective observations
Total carriers
3
0 BrS1 · 0 LQT3 · 3 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 (%) |
|---|---|---|---|---|---|
| 1.29 | 0.629 | 1.26 | 0.368 | 0 | 2 |
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 |
|---|---|---|---|---|---|---|---|
| 18088563 | 2008 | 3 | 0 | 0 | 3 | SSS, AF | |
| Literature, cohort, and gnomAD | – | 3 | 3 | 0 | 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) |
|---|---|---|---|---|---|---|
| 18088563 | 2008 | Oocytes | 111 | -3.4 | 100 |
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 |
|---|---|---|
| 1972 | 15 | |
| 1973 | 14 | F1973L, |
| 1974 | 14 | |
| 1975 | 13 | P1975T, |
| 1976 | 13 | S1976C, |
| 1977 | 12 | Y1977N, |
| 1978 | 11 | |
| 1979 | 11 | |
| 1980 | 10 | V1980F, |
| 1981 | 9 | |
| 1982 | 8 | R1982T, |
| 1983 | 8 | A1983G, A1983V, |
| 1984 | 7 | T1984I, |
| 1985 | 5 | S1985R, |
| 1986 | 4 | D1986G, D1986N, |
| 1987 | 0 | N1987K, |
| 1988 | 4 | L1988R, |
| 1989 | 5 | |
| 1990 | 7 | V1990L, |
| 1991 | 8 | R1991Q, R1991W, |
| 1992 | 8 | G1992A, |
| 1993 | 9 | |
| 1994 | 10 | |
| 1995 | 11 | Y1995X, |
| 1996 | 11 | S1996R, S1996N, |
| 1997 | 12 | H1997R, |
| 1998 | 13 | |
| 1999 | 13 | |
| 2000 | 14 | D2000Y, |
| 2001 | 14 | |
| 2002 | 15 | A2002T, |