SCN5A Variant N1463Y

Summary of observed carriers, functional annotations, and structural context for SCN5A N1463Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

53%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

N1463Y has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
-7.64 0.889 -4.06 0.951 70 6

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
20129283 2010 1 0 1 0
29325976 2018 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
20129283 2010
29325976 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.

Previously observed variants near N1463Y.
Neighbour residue Distance (Å) Observed variants
939 10 L939F,
896 12 C896S, C896S,
937 10
895 13 L895F,
1417 11
1765 9
839 13 L839P,
842 13
1340 13 V1340I,
1457 8
1453 13
1757 14
1455 11
1756 14 I1756V,
1461 6 T1461S, T1461S,
926 14
1764 12 c.5290delG, V1764F,
409 11 L409V, L409P,
1333 15
1344 14 F1344L, F1344S, F1344L, F1344L,
928 14 L928P,
934 7
1458 7 S1458Y,
933 11
1471 13
935 6 L935P,
412 14 V412D,
897 14 G897R, G897R, G897E,
1762 12 p.I1762del, I1762M,
1470 11
1464 5 c.4389_4396delCCTCTTTA, L1464P,
927 12 N927S, N927K, N927K,
1466 6 c.4396_4397insG,
1769 13
1418 12
1766 14 M1766L, M1766V, M1766L, M1766T,
1768 11 I1768V,
940 14 S940N,
1334 13 I1334V,
1341 11
1468 10 V1468F, V1468A,
405 13
831 15
1462 4
938 7
1759 15 S1759C,
942 11
843 14 T843A,
1456 11
930 12 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 7 c.4376_4379delTCTT,
1772 14 L1772V
1460 7 F1460L, F1460L, F1460L,
1454 11
1338 13 L1338V,
410 15 A410V,
929 14
416 15 Y416C,
413 14 A413T, A413E,
1345 13 W1345C, W1345C,
941 13 S941N, S941F,
1337 11
846 15 L846R,
936 10
1763 15 V1763M, V1763L, V1763L,
1416 10 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1465 7 p.F1465_L1480dup,
1760 10
1467 8
1761 9 c.5280delG, L1761F, L1761H,
1469 11 I1469V,
406 13 N406S, N406K, N406K,
1710 14 S1710L,
1415 14
932 9
832 14
835 15 S835A, S835L,
828 14 L828V,
931 8
1463 0 N1463Y,
1413 14