SCN5A Variant Q912R
Summary of observed carriers, functional annotations, and structural context for SCN5A Q912R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
31%
2/12 effective observations
Estimated BrS1 penetrance
13%
1/12 effective observations
Total carriers
2
0 BrS1 · 1 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.72 | 0.106 | -0.19 | 0.726 | 14 | 32 |
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 |
|---|---|---|---|---|---|---|---|
| 23631430 | 2013 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 1 | 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) |
|---|---|---|---|---|---|---|
| 23631430 | 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 |
|---|---|---|
| 364 | 14 | |
| 919 | 12 | |
| 363 | 11 | |
| 360 | 8 | |
| 356 | 15 | D356N, |
| 361 | 14 | |
| 904 | 9 | W904X, |
| 864 | 13 | |
| 354 | 14 | |
| 909 | 9 | |
| 868 | 14 | c.2602delC, L868X, |
| 902 | 13 | |
| 349 | 15 | D349N, |
| 357 | 13 | |
| 860 | 14 | p.L860fsx89, |
| 362 | 14 | |
| 911 | 4 | G911E, |
| 920 | 13 | |
| 900 | 13 | |
| 918 | 12 | |
| 917 | 10 | L917V, L917R |
| 865 | 14 | |
| 913 | 5 | |
| 916 | 7 | |
| 912 | 0 | Q912R, |
| 347 | 14 | |
| 906 | 8 | |
| 351 | 10 | G351S, G351C, G351D, G351V, |
| 910 | 7 | S910L, |
| 350 | 11 | H350Q, H350Q, |
| 903 | 9 | p.M903CfsX29, |
| 346 | 15 | E346K, E346G, E346X, E346D, E346D, |
| 359 | 10 | A359T, p.A359PfsX12, |
| 905 | 11 | |
| 352 | 7 | Y352C, |
| 915 | 7 | C915R, |
| 899 | 14 | |
| 908 | 9 | |
| 914 | 8 | |
| 861 | 12 | p.F861WfsX90, c.2582_2583delTT, |
| 353 | 13 | T353I, |
| 907 | 4 |