SCN5A Variant V263I
Summary of observed carriers, functional annotations, and structural context for SCN5A V263I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
27%
2/13 effective observations
Estimated BrS1 penetrance
2%
0/13 effective observations
Total carriers
3
0 BrS1 · 1 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.98 | 0.999 | 6.69 | 0.767 | 1 | 24 |
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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 2 | 1 | 0 | – | |
| Variant features alone | – | 15 | 14 | 1 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
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 |
|---|---|---|
| 403 | 14 | |
| 364 | 13 | |
| 271 | 12 | L271V, |
| 266 | 6 | L266H, |
| 363 | 15 | |
| 404 | 13 | L404V, L404Q, |
| 1544 | 13 | T1544P, |
| 270 | 11 | Q270K, |
| 1627 | 7 | |
| 396 | 10 | V396L, V396A, |
| 1624 | 10 | V1624I, |
| 355 | 12 | F355I, F355C, |
| 1538 | 12 | |
| 391 | 15 | |
| 254 | 15 | |
| 401 | 14 | S401P, |
| 1634 | 12 | L1634P |
| 1543 | 11 | V1543L, V1543L, V1543A, |
| 1542 | 7 | |
| 361 | 11 | |
| 260 | 6 | |
| 366 | 13 | |
| 365 | 9 | |
| 258 | 9 | V258A, |
| 1546 | 9 | M1546T, |
| 369 | 12 | M369K, |
| 1545 | 10 | |
| 1630 | 7 | I1630V, I1630R, |
| 1626 | 12 | R1626C, R1626H, R1626P, R1626L, |
| 267 | 6 | |
| 1625 | 13 | |
| 262 | 4 | S262G, |
| 357 | 15 | |
| 256 | 11 | |
| 399 | 11 | |
| 272 | 14 | |
| 397 | 14 | I397V, I397F, I397T, |
| 362 | 10 | |
| 261 | 7 | |
| 1628 | 8 | |
| 1632 | 13 | R1632C, R1632H, R1632L, |
| 1539 | 11 | C1539Y, C1539F, |
| 392 | 11 | |
| 255 | 13 | |
| 269 | 11 | |
| 395 | 10 | |
| 393 | 14 | |
| 1535 | 14 | |
| 264 | 4 | |
| 259 | 6 | |
| 1633 | 11 | |
| 1591 | 14 | W1591X, |
| 1548 | 15 | E1548K, G1548K, |
| 265 | 6 | A265V, |
| 358 | 10 | |
| 263 | 0 | V263I, |
| 359 | 14 | A359T, p.A359PfsX12, |
| 1629 | 12 | R1629G, R1629X, R1629Q, |
| 1547 | 15 | V1547L, V1547L, |
| 1541 | 12 | |
| 1540 | 14 | |
| 1631 | 9 | G1631D, |
| 368 | 13 | |
| 268 | 9 | G268S, |
| 257 | 10 | |
| 400 | 11 | G400R, G400R, G400E, G400A, |
| 1623 | 12 | c.4867delC, R1623X, R1623Q, R1623L, |