SCN5A Variant T1620M
Summary of observed carriers, functional annotations, and structural context for SCN5A T1620M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
19%
3/21 effective observations
Estimated BrS1 penetrance
39%
8/21 effective observations
Total carriers
11
6 BrS1 · 1 LQT3 · 4 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.32 | 0.994 | 0.11 | 0.951 | 28 | 53 |
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 |
|---|---|---|---|---|---|---|---|
| 10662748 | 2000 | 8 | 0 | 6 | 0 | ||
| 15520322 | 2004 | 4 | 0 | 4 | 0 | ||
| 25163546 | 2015 | 1 | 0 | 0 | 1 | DCM | |
| 26669661 | 2016 | 2 | 1 | 0 | 0 | ||
| 9521325 | 1998 | 7 | 0 | 7 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 11 | 4 | 1 | 6 | – | |
| Variant features alone | – | 15 | 11 | 2 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 11786529 | 2002 | HEK-tSA202 | 80 | -2.3 | -8.5 | |
| 10664447 | 2000 | HEK | 100 | NA | 0 | 0 |
| 10662748 | 2000 | |||||
| 15520322 | 2004 | |||||
| 25163546 | 2015 | |||||
| 26669661 | 2016 | |||||
| 10532948 | 1999 | |||||
| 11013131 | 2000 | |||||
| 11417215 | 2001 | |||||
| 18503232 | 2008 | |||||
| 11029409 | 2000 | HEK-tSA201 | 0 | 6.2 | ||
| 9521325 | 1998 | Xeno | ||||
| 20129283 | 2010 | |||||
| 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 |
|---|---|---|
| 271 | 6 | L271V, |
| 266 | 12 | L266H, |
| 270 | 8 | Q270K, |
| 1627 | 11 | |
| 385 | 12 | A385T, |
| 1624 | 7 | V1624I, |
| 355 | 14 | F355I, F355C, |
| 391 | 12 | |
| 388 | 11 | I388S, |
| 1602 | 14 | |
| 1601 | 11 | L1601H, |
| 1613 | 12 | Q1613L, Q1613H, Q1613H, |
| 1615 | 15 | Y1615X, |
| 384 | 15 | S384T, |
| 329 | 14 | |
| 386 | 13 | G386R, G386R, G386E, |
| 1545 | 12 | |
| 1626 | 11 | R1626C, R1626H, R1626P, R1626L |
| 267 | 10 | |
| 1625 | 9 | |
| 1610 | 15 | D1610G, |
| 272 | 10 | |
| 274 | 14 | G274C, |
| 273 | 12 | |
| 1628 | 13 | |
| 1597 | 14 | V1597M, |
| 392 | 12 | |
| 389 | 10 | Y389H, Y389X, |
| 269 | 12 | |
| 1620 | 0 | T1620K, T1620M, |
| 395 | 15 | |
| 275 | 12 | N275K, N275K, |
| 264 | 14 | |
| 1614 | 11 | |
| 1548 | 14 | E1548K, G1548K, |
| 265 | 15 | A265V, |
| 1619 | 4 | P1619Q, P1619L, c.4856delC, |
| 1605 | 13 | c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D, |
| 1616 | 13 | |
| 1617 | 8 | p.F1617del, |
| 268 | 11 | G268S, |
| 1604 | 14 | c.4810+3_4810+6dupGGGT, V1604M, |
| 1622 | 7 | |
| 1618 | 5 | |
| 1621 | 4 | |
| 1598 | 13 | V1598A, |
| 1623 | 5 | c.4867delC, R1623X, R1623Q, R1623L, |