SCN5A Variant G752R
Summary of observed carriers, functional annotations, and structural context for SCN5A G752R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/20 effective observations
Estimated BrS1 penetrance
59%
11/20 effective observations
Total carriers
10
8 BrS1 · 0 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.66 | 0.981 | -3.37 | 0.974 | 47 | 8 |
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 |
|---|---|---|---|---|---|---|---|
| 12693506 | 2003 | 6 | 0 | 5 | 0 | ||
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 20031634 | 2009 | 6 | 0 | 4 | 0 | ||
| 22885917 | 2012 | 2 | 0 | 2 | 0 | ||
| 24365614 | 2014 | 1 | 0 | 0 | 1 | Aflutter | |
| 20022821 | 2010 | 2 | 0 | 2 | 0 | ||
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 10 | 2 | 0 | 8 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 19251209 | 2009 | |||||
| 20042374 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20022821 | 2010 | |||||
| 20129283 | 2010 | |||||
| 32533946 | 2020 | HEK | 23 | 22.6 | ||
| 12106943 | 2002 | |||||
| 16643399 | 2006 | |||||
| 20031634 | 2009 | |||||
| 22885917 | 2012 | |||||
| 24365614 | 2014 | |||||
| 12693506 | 2003 | COS | 6 | 30 | -10 |
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 |
|---|---|---|
| 723 | 14 | I723V, |
| 758 | 10 | G758E, |
| 811 | 10 | R811H, R811G, c.2435_2436+3delTGGTAinsCGCCT, |
| 733 | 6 | F733L, F733L, F733L, |
| 741 | 14 | p.M741_T742delinsI , |
| 808 | 13 | R808C, R808H, R808P, |
| 745 | 11 | |
| 746 | 12 | E746K, |
| 760 | 11 | p.F760SfsX5, |
| 759 | 10 | p.I759FfsX6, I759V, c.2274delG, |
| 792 | 12 | |
| 755 | 5 | |
| 731 | 11 | T731I, |
| 800 | 15 | R800L, R800C, R800H, |
| 754 | 5 | |
| 726 | 10 | |
| 737 | 12 | |
| 750 | 6 | Q750R, |
| 749 | 6 | |
| 743 | 14 | |
| 793 | 14 | L793F, |
| 728 | 13 | V728I, |
| 762 | 15 | |
| 747 | 9 | E747A, |
| 727 | 12 | |
| 735 | 13 | A735V, A735T, A735E, |
| 732 | 11 | |
| 734 | 10 | c.2201dupT, M734V, |
| 756 | 5 | |
| 814 | 11 | R814Q, |
| 757 | 8 | |
| 761 | 13 | |
| 744 | 14 | |
| 752 | 0 | G752R, G752R, |
| 725 | 14 | |
| 751 | 4 | V751I, V751F, |
| 796 | 11 | |
| 736 | 12 | L736P, |
| 730 | 7 | N730K, N730K, |
| 789 | 15 | V789A, V789I, |
| 753 | 4 | |
| 729 | 9 | p.L729del, |
| 795 | 13 | |
| 748 | 7 | M748I, M748I, M748I, |
| 799 | 14 |