SCN5A Variant M28L
Summary of observed carriers, functional annotations, and structural context for SCN5A M28L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/16 effective observations
Estimated BrS1 penetrance
1%
0/16 effective observations
Total carriers
6
0 BrS1 · 0 LQT3 · 6 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
0.49 | 0 | -0.61 | 0.164 | 0 | 4 |
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 |
---|---|---|---|---|---|---|---|
Literature, cohort, and gnomAD | – | 6 | 6 | 0 | 0 | – | |
Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
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 |
---|---|---|
13 | 15 | |
14 | 14 | R14C, R14H, R14S, |
15 | 14 | R15G, R15T, R15M, |
16 | 13 | F16L, F16L, F16L, |
17 | 13 | |
18 | 12 | R18W, R18Q, |
19 | 11 | |
20 | 11 | S20F, |
21 | 10 | L21V, |
22 | 9 | A22V, |
23 | 8 | A23S, |
24 | 8 | |
25 | 7 | E25K, |
26 | 5 | |
27 | 4 | R27L, R27H, R27C, |
28 | 0 | M28I, M28I, M28L, M28T, M28L, M28I, |
29 | 4 | A29E, A29V, |
30 | 5 | E30G, |
31 | 7 | |
32 | 8 | |
33 | 8 | |
34 | 9 | R34H, R34C, |
35 | 10 | G35S, |
36 | 11 | |
37 | 11 | T37A, |
38 | 12 | |
39 | 13 | L39F, L39F, |
40 | 13 | |
41 | 14 | |
42 | 14 | |
43 | 15 | R43Q, R43X, |