SCN5A Variant c.2549_2550insTG
Summary of observed carriers, functional annotations, and structural context for SCN5A c.2549_2550insTG. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
13%
0/11 effective observations
Estimated BrS1 penetrance
39%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 45 | 18 |
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 | 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) |
|---|---|---|---|---|---|---|
| 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 | 6 | I891N, I891T, |
| 888 | 6 | |
| 848 | 7 | I848F, |
| 223 | 11 | V223L, |
| 856 | 10 | V856L, V856L, |
| 890 | 10 | I890T, |
| 919 | 12 | |
| 896 | 11 | C896S, C896S, |
| 895 | 8 | L895F, |
| 842 | 12 | |
| 894 | 9 | I894M, |
| 1455 | 13 | |
| 1447 | 13 | |
| 149 | 14 | |
| 926 | 8 | |
| 928 | 14 | L928P, |
| 925 | 10 | I925F, |
| 227 | 12 | L227P, |
| 887 | 9 | |
| 1451 | 12 | V1451L, V1451D, |
| 886 | 14 | H886P, H886Q, H886Q, |
| 933 | 15 | |
| 229 | 13 | |
| 851 | 6 | c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L, |
| 897 | 13 | G897R, G897R, G897E, |
| 924 | 13 | V924I, |
| 927 | 12 | N927S, N927K, N927K, |
| 852 | 6 | |
| 854 | 6 | c.2559delT, |
| 224 | 13 | L224F, |
| 845 | 9 | c.2533delG, |
| 857 | 11 | G857D, |
| 902 | 15 | |
| 892 | 8 | F892I, |
| 881 | 13 | |
| 849 | 5 | |
| 226 | 11 | A226G, A226V, |
| 898 | 15 | |
| 893 | 13 | R893C, R893H, |
| 921 | 12 | |
| 922 | 8 | V922I, |
| 860 | 15 | p.L860fsx89, |
| 920 | 15 | |
| 840 | 15 | |
| 889 | 10 | |
| 843 | 11 | T843A, |
| 930 | 10 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 13 | c.4376_4379delTCTT |
| 858 | 12 | M858L, M858L, |
| 918 | 12 | |
| 855 | 9 | |
| 1454 | 14 | |
| 230 | 13 | I230V, I230T, I230M, |
| 148 | 13 | |
| 929 | 13 | |
| 1448 | 14 | I1448L, I1448T, |
| 884 | 10 | |
| 885 | 12 | |
| 847 | 5 | |
| 846 | 6 | L846R, |
| 853 | 5 | |
| 923 | 12 | |
| 883 | 14 | |
| 844 | 11 | L844RfsX3, |
| 850 | 0 | V850M, c.2549_2550insTG, |
| 243 | 14 | |
| 145 | 12 | |
| 861 | 15 | p.F861WfsX90, c.2582_2583delTT, |
| 931 | 12 |