SCN5A Variant I1469V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1469V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1469V is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.97 0.013 4.93 0.746 19 15

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 0 1

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 I1469V.
Neighbour residue Distance (Å) Observed variants
1328 11 V1328M,
939 10 L939F,
1773 10
1765 6
943 13 S943N,
1757 12
1472 5 p.N1472del, N1472S,
1771 12 I1771T,
1461 13 T1461S, T1461S,
1320 15 M1320I, M1320I, M1320I,
1764 10 c.5290delG, V1764F,
409 13 L409V, L409P,
1333 9
1656 14
1477 12 K1477N, K1477N,
1471 7
935 11 L935P,
1762 7 p.I1762del, I1762M,
1470 5
1464 9 c.4389_4396delCCTCTTTA, L1464P,
1466 5 c.4396_4397insG,
1478 15 K1478E,
944 13
1767 11 Y1767C,
1660 12 I1660V, I1660S,
1329 9 G1329S,
1769 6
402 15 F402L, F402L, F402L,
1766 6 M1766L, M1766V, M1766L, M1766T,
1768 8 I1768V,
940 15 S940N,
1774 14 N1774D, c.5321_5324dupACTT
1479 15
1473 6 F1473S, F1473C,
1334 8 I1334V,
1468 5 V1468F, V1468A,
1663 14
1657 14
1462 12
1474 10
1759 12 S1759C,
938 12
1324 12
1327 9
942 12
1758 12 I1758V, p.I1758del,
1330 7 A1330T, A1330P, A1330D,
1772 10 L1772V,
1460 15 F1460L, F1460L, F1460L,
1323 11 V1323G,
1338 13 L1338V,
410 15 A410V,
1770 10 I1770V,
1322 12 c.3963+2T>C, c.3963+4A>G,
941 15 S941N, S941F,
1337 11
1326 8 A1326S,
936 14
1763 9 V1763M, V1763L, V1763L,
1332 12 P1332Q, P1332L,
1465 7 p.F1465_L1480dup,
1760 12
1467 5
1476 11 Q1476X, Q1476R,
1331 10 I1331V,
1761 9 c.5280delG, L1761F, L1761H,
1475 12 p.Q1475NfsX6, Q1475L,
1469 0 I1469V,
406 13 N406S, N406K, N406K,
1336 13
1325 12 N1325S,
1335 13 M1335R,
1463 11 N1463Y,