SCN5A Variant F2004L
Summary of observed carriers, functional annotations, and structural context for SCN5A F2004L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
2/30 effective observations
Estimated BrS1 penetrance
22%
6/30 effective observations
Total carriers
20
5 BrS1 · 2 LQT3 · 13 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.63 | 0 | -0.21 | 0.29 | 23 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 18456723 | 2008 | 5 | 0 | 1 | 0 | ||
| 17210841 | 2007 | 3 | 0 | 0 | 3 | SIDS | |
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 22677073 | 2012 | 1 | 0 | 0 | 1 | SUDS | |
| 23714088 | 2013 | 1 | 1 | 0 | 0 | ||
| 23936059 | 2013 | 1 | 1 | 0 | 0 | ||
| 25163546 | 2015 | 1 | 0 | 0 | 1 | DCM | |
| 21126620 | 2010 | 1 | 0 | 1 | 0 | ||
| 23571586 | 2013 | 1 | 0 | 0 | 1 | stillbirth, SUDS | |
| 22685113 | 2012 | 1 | 0 | 0 | 1 | AF | |
| 18071069 | 2008 | 1 | 0 | 0 | 1 | SCD | |
| 20129283 | 2010 | 7 | 0 | 0 | 0 | ||
| 29672598 | 2018 | 1 | 0 | 0 | 1 | SUDS | |
| 29672598 | 2018 | 2 | 0 | 2 | 1 | SUDS | |
| Literature, cohort, and gnomAD | – | 20 | 13 | 2 | 5 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 25163546 | 2015 | |||||
| 29017927 | 2017 | |||||
| 21126620 | 2010 | |||||
| 23465283 | 2013 | |||||
| 23571586 | 2013 | |||||
| 17646591 | 2007 | |||||
| 22685113 | 2012 | HEK | ||||
| 18071069 | 2008 | Xeno | ||||
| 20129283 | 2010 | |||||
| 17210841 | 2007 | tsA202 | 120 | 0.7 | 4.7 | 386 |
| 22677073 | 2012 | |||||
| 29672598 | 2018 | |||||
| 29672598 | 2018 | |||||
| 16643399 | 2006 | |||||
| 18456723 | 2008 | CHO | 57 | |||
| 23414114 | 2013 | |||||
| 23714088 | 2013 | |||||
| 23936059 | 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 |
|---|---|---|
| 1989 | 15 | |
| 1990 | 14 | V1990L, |
| 1991 | 14 | R1991Q, R1991W, |
| 1992 | 13 | G1992A, |
| 1993 | 13 | |
| 1994 | 12 | |
| 1995 | 11 | Y1995X, |
| 1996 | 11 | S1996R, S1996N, |
| 1997 | 10 | H1997R, |
| 1998 | 9 | |
| 1999 | 8 | |
| 2000 | 8 | D2000Y, |
| 2001 | 7 | |
| 2002 | 5 | A2002T, |
| 2003 | 4 | D2003N, |
| 2004 | 0 | F2004I, F2004L, F2004V, p.F2004dup, |
| 2005 | 4 | P2005A, P2005L, P2005S |
| 2006 | 5 | p.P2006LfsX32, P2006A, p.Pro2006del, P2006T, |
| 2007 | 7 | p.S2007FfsX7, |
| 2008 | 8 | P2008L, |
| 2009 | 8 | D2009E, |
| 2010 | 9 | R2010G, |
| 2011 | 10 | |
| 2012 | 11 | R2012C, R2012H, |
| 2013 | 11 | |
| 2014 | 12 | |
| 2015 | 13 | |
| 2016 | 13 | V2016L, V2016M, |