SCN5A Variant c.2788-6C>T
Summary of observed carriers, functional annotations, and structural context for SCN5A c.2788-6C>T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
1/45 effective observations
Estimated BrS1 penetrance
3%
1/45 effective observations
Total carriers
35
0 BrS1 · 0 LQT3 · 35 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 10 | 42 |
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 |
|---|---|---|---|---|---|---|---|
| 25051102 | 2014 | 38 | 0 | 0 | 3 | VF | |
| Literature, cohort, and gnomAD | – | 35 | 35 | 0 | 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) |
|---|---|---|---|---|---|---|
| 25051102 | 2014 |
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 |
|---|---|---|
| 414 | 15 | M414V, |
| 891 | 13 | I891N, I891T, |
| 848 | 11 | I848F, |
| 939 | 14 | L939F, |
| 896 | 11 | C896S, C896S, |
| 937 | 10 | |
| 895 | 8 | L895F, |
| 839 | 11 | L839P, |
| 842 | 7 | |
| 894 | 13 | I894M, |
| 247 | 11 | V247L, V247L, |
| 240 | 11 | V240M, |
| 1455 | 12 | |
| 926 | 5 | |
| 250 | 13 | |
| 409 | 11 | L409V, L409P, |
| 928 | 8 | L928P, |
| 925 | 7 | I925F, |
| 227 | 15 | L227P, |
| 934 | 7 | |
| 1458 | 13 | S1458Y, |
| 933 | 5 | |
| 246 | 10 | |
| 935 | 9 | L935P, |
| 412 | 9 | V412D, |
| 897 | 13 | G897R, G897R, G897E, |
| 924 | 9 | V924I, |
| 927 | 7 | N927S, N927K, N927K, |
| 852 | 14 | |
| 245 | 14 | Q245K, |
| 845 | 8 | c.2533delG, |
| 244 | 12 | |
| 415 | 12 | A415T, |
| 892 | 13 | F892I, |
| 849 | 8 | |
| 921 | 13 | |
| 922 | 10 | V922I, |
| 405 | 13 | |
| 938 | 12 | |
| 241 | 12 | |
| 920 | 15 | |
| 840 | 12 | |
| 843 | 9 | T843A, |
| 930 | 0 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 10 | c.4376_4379delTCTT, |
| 1460 | 14 | F1460L, F1460L, F1460L, |
| 239 | 9 | I239V, I239V , |
| 1454 | 14 | |
| 230 | 13 | I230V, I230T, I230M, |
| 410 | 14 | A410V, |
| 242 | 10 | A242D, |
| 929 | 4 | |
| 416 | 11 | Y416C, |
| 413 | 12 | A413T, A413E, |
| 841 | 12 | p.N841TfsX2, N841K, N841K, |
| 236 | 14 | |
| 408 | 11 | |
| 847 | 10 | |
| 846 | 6 | L846R, |
| 936 | 10 | |
| 238 | 13 | |
| 233 | 15 | |
| 838 | 13 | |
| 853 | 12 | |
| 923 | 10 | |
| 406 | 15 | N406S, N406K, N406K, |
| 844 | 12 | L844RfsX3, |
| 850 | 10 | V850M, c.2549_2550insTG, |
| 411 | 13 | V411M, |
| 243 | 7 | |
| 932 | 6 | |
| 931 | 4 | |
| 1463 | 12 | N1463Y |