SCN5A Variant I1770V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1770V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

20%

1/11 effective observations

Estimated BrS1 penetrance

3%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1770V is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
0.21 0.78 6.3 0.584 6 26

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

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 1 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.

Previously observed variants near I1770V.
Neighbour residue Distance (Å) Observed variants
403 10
939 15 L939F,
1659 10
404 14 L404V, L404Q,
1778 13
1480 13 c.4438-1C>T, c.4437+5G>A,
1773 6
1765 10
1653 6
1472 12 p.N1472del, N1472S,
1771 5 I1771T,
401 14 S401P,
1652 9 M1652T, M1652R,
1777 11 V1777L, V1777M,
1320 12 M1320I,
1764 11 c.5290delG, V1764F,
409 12 L409V, L409P,
1650 10 L1650F,
1656 6
1477 8 K1477N,
1471 12
1779 15 T1779M,
1762 13 I1762M, p.I1762del,
1470 9
1466 11 c.4396_4397insG,
1478 14 K1478E,
1776 11
1767 6 Y1767C,
1660 8 I1660V, I1660S,
1654 10
1648 13
1769 4
402 11 F402L,
1766 7 M1766L, M1766V, M1766T,
1319 11 G1319V,
1649 10 A1649V,
1768 7 I1768V,
1774 6 N1774D, c.5321_5324dupACTT,
1473 6 F1473C, F1473S,
1468 14 V1468F, V1468A,
1663 13
399 14
405 13
1657 6
1474 10
1662 14
1324 13
1327 13
1318 14
1330 15 A1330P, A1330D, A1330T,
1772 7 L1772V,
1323 9 V1323G,
410 11 A410V,
1770 0 I1770V,
1651 13
413 15 A413E, A413T,
408 15
1322 9 c.3963+2T>C, c.3963+4A>G,
407 12
1326 11 A1326S,
1763 11 V1763L, V1763M,
1467 13
1476 11 Q1476X, Q1476R,
1775 11 p.F1775LfsX15, F1775V,
1661 12 G1661E, G1661R,
1655 9
1475 14 Q1475L, p.Q1475NfsX6,
1469 10 I1469V,
406 9 N406S, N406K,
1325 14 N1325S,
398 12
1647 15
400 14 G400R, G400A, G400E,
1646 14
1664 13
1658 11