SCN5A Variant R1991Q
Summary of observed carriers, functional annotations, and structural context for SCN5A R1991Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
15%
1/14 effective observations
Estimated BrS1 penetrance
3%
0/14 effective observations
Total carriers
4
0 BrS1 · 1 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 (%) |
|---|---|---|---|---|---|
| -0.29 | 0.001 | 2.04 | 0.573 | 0 | 9 |
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 |
|---|---|---|---|---|---|---|---|
| 27566755 | 2016 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 0 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 4 | 3 | 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.
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 |
|---|---|---|
| 1976 | 15 | S1976C, |
| 1977 | 14 | Y1977N, |
| 1978 | 14 | |
| 1979 | 13 | |
| 1980 | 13 | V1980F, |
| 1981 | 12 | |
| 1982 | 11 | R1982T, |
| 1983 | 11 | A1983G, A1983V, |
| 1984 | 10 | T1984I, |
| 1985 | 9 | S1985R, |
| 1986 | 8 | D1986G, D1986N, |
| 1987 | 8 | N1987K, |
| 1988 | 7 | L1988R, |
| 1989 | 5 | |
| 1990 | 4 | V1990L, |
| 1991 | 0 | R1991Q, R1991W, |
| 1992 | 4 | G1992A, |
| 1993 | 5 | |
| 1994 | 7 | |
| 1995 | 8 | Y1995X, |
| 1996 | 8 | S1996R, S1996N, |
| 1997 | 9 | H1997R, |
| 1998 | 10 | |
| 1999 | 11 | |
| 2000 | 11 | D2000Y, |
| 2001 | 12 | |
| 2002 | 13 | A2002T, |
| 2003 | 13 | D2003N, |
| 2004 | 14 | F2004I, F2004L, F2004V, p.F2004dup, |
| 2005 | 14 | P2005A, P2005L, P2005S, |
| 2006 | 15 | p.P2006LfsX32, P2006A, p.Pro2006del, P2006T, |