SCN5A Variant M748I
Summary of observed carriers, functional annotations, and structural context for SCN5A M748I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
12%
0/11 effective observations
Estimated BrS1 penetrance
7%
0/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -0.78 | 0.002 | 2.5 | 0.582 | 7 | 17 |
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 | – | 1 | 1 | 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 |
|---|---|---|
| 737 | 10 | |
| 747 | 6 | E747A, |
| 811 | 14 | R811G, c.2435_2436+3delTGGTAinsCGCCT, R811H, |
| 735 | 12 | A735E, A735T, A735V, |
| 733 | 7 | F733L, |
| 751 | 6 | V751I, V751F, |
| 754 | 11 | |
| 736 | 9 | L736P, |
| 732 | 11 | |
| 741 | 10 | p.M741_T742delinsI , |
| 808 | 15 | R808P, R808C, R808H, |
| 745 | 5 | |
| 734 | 12 | c.2201dupT, M734V, |
| 756 | 11 | |
| 730 | 11 | N730K, |
| 750 | 8 | Q750R, |
| 753 | 9 | |
| 729 | 11 | p.L729del, |
| 749 | 4 | |
| 757 | 15 | |
| 746 | 8 | E746K, |
| 743 | 9 | |
| 748 | 0 | M748I, |
| 738 | 13 | |
| 744 | 7 | |
| 742 | 9 | T742A, |
| 752 | 7 | G752R, |
| 755 | 11 | |
| 740 | 14 | p.N740del, |
| 731 | 13 | T731I, |
| 726 | 15 |