SCN5A Variant C915R
Summary of observed carriers, functional annotations, and structural context for SCN5A C915R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
10%
0/11 effective observations
Estimated BrS1 penetrance
59%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -10.92 | 0.998 | -3.51 | 0.961 | 80 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 891 | 12 | I891N, I891T, |
| 880 | 14 | |
| 856 | 11 | V856L, V856L, |
| 890 | 11 | I890T, |
| 901 | 12 | E901K, S901L, |
| 919 | 6 | |
| 862 | 11 | |
| 363 | 12 | |
| 859 | 13 | |
| 360 | 13 | |
| 894 | 12 | I894M, |
| 863 | 14 | |
| 904 | 9 | W904X, |
| 887 | 13 | |
| 366 | 15 | |
| 864 | 11 | |
| 909 | 9 | |
| 854 | 13 | c.2559delT, |
| 857 | 9 | G857D, |
| 868 | 14 | c.2602delC, L868X, |
| 902 | 8 | |
| 881 | 10 | |
| 893 | 14 | R893C, R893H, |
| 921 | 11 | |
| 922 | 11 | V922I |
| 860 | 8 | p.L860fsx89, |
| 911 | 7 | G911E, |
| 920 | 9 | |
| 900 | 11 | |
| 858 | 13 | M858L, M858L, |
| 918 | 6 | |
| 855 | 15 | |
| 917 | 7 | L917V, L917R, |
| 865 | 11 | |
| 913 | 6 | |
| 916 | 5 | |
| 912 | 7 | Q912R, |
| 906 | 4 | |
| 351 | 15 | G351S, G351C, G351D, G351V, |
| 910 | 7 | S910L, |
| 350 | 13 | H350Q, H350Q, |
| 903 | 6 | p.M903CfsX29, |
| 367 | 15 | R367C, R367H, R367L, |
| 359 | 15 | A359T, p.A359PfsX12, |
| 853 | 12 | |
| 877 | 15 | |
| 923 | 13 | |
| 905 | 9 | |
| 352 | 12 | Y352C, |
| 915 | 0 | C915R, |
| 899 | 11 | |
| 908 | 10 | |
| 914 | 5 | |
| 861 | 6 | p.F861WfsX90, c.2582_2583delTT, |
| 220 | 14 | T220I, |
| 907 | 5 |