SCN5A Variant R2012H
Summary of observed carriers, functional annotations, and structural context for SCN5A R2012H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/20 effective observations
Estimated BrS1 penetrance
10%
2/20 effective observations
Total carriers
10
1 BrS1 · 0 LQT3 · 9 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 (%) |
|---|---|---|---|---|---|
| -1.26 | 0.999 | -2.4 | 0.483 | 5 | 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 |
|---|---|---|---|---|---|---|---|
| 27287068 | 2016 | 2 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 10 | 9 | 0 | 1 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 27287068 | 2016 | Oocytes | 75 |
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 |
|---|---|---|
| 1997 | 15 | H1997R, |
| 1998 | 14 | |
| 1999 | 14 | |
| 2000 | 13 | D2000Y, |
| 2001 | 13 | |
| 2002 | 12 | A2002T, |
| 2003 | 11 | D2003N, |
| 2004 | 11 | F2004I, F2004L, F2004V, p.F2004dup, |
| 2005 | 10 | P2005A, P2005L, P2005S |
| 2006 | 9 | p.P2006LfsX32, P2006A, p.Pro2006del, P2006T, |
| 2007 | 8 | p.S2007FfsX7, |
| 2008 | 8 | P2008L, |
| 2009 | 7 | D2009E, |
| 2010 | 5 | R2010G, |
| 2011 | 4 | |
| 2012 | 0 | R2012C, R2012H, |
| 2013 | 4 | |
| 2014 | 5 | |
| 2015 | 7 | |
| 2016 | 8 | V2016L, V2016M, |