SCN5A Variant G1661E

Summary of observed carriers, functional annotations, and structural context for SCN5A G1661E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

36%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G1661E is present in 1 alleles 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 3 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 (%)
-7.49 0.999 -4.46 0.974 52 2

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 12 0 3 – –

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 G1661E.
Neighbour residue Distance (Å) Observed variants
403 12
1659 6
1765 13
396 15 V396L, V396A,
1653 12
391 14
1315 13
1771 14 I1771T
401 14 S401P,
1314 10 c.3940_3941delCT,
1320 9 M1320I, M1320I, M1320I,
1764 10 c.5290delG, V1764F,
1666 9
1656 9
1704 13 L1704H,
1669 12
1671 15
1762 13 p.I1762del, I1762M,
1668 9 M1668T,
1767 8 Y1767C,
1313 14
1660 4 I1660V, I1660S,
1654 11
1310 14
1769 14
402 10 F402L, F402L, F402L,
1766 10 M1766L, M1766V, M1766L, M1766T,
1319 11 G1319V,
1665 7
1768 13 I1768V,
1473 15 F1473S, F1473C,
1663 5
399 11
397 12 I397V, I397F, I397T,
1657 7
1759 11 S1759C,
1662 4
1324 13
1317 11 F1317C,
1327 13
1709 13 p.T1709del, T1709R, T1709M,
1701 13 M1701I, M1701I, M1701I,
1758 13 I1758V, p.I1758del,
1755 14
1318 14
395 13
1323 10 V1323G,
394 10
390 14
1770 12 I1770V,
1708 11 T1708I,
1705 11
1322 13 c.3963+2T>C, c.3963+4A>G,
1326 15 A1326S,
1763 9 V1763M, V1763L, V1763L,
1311 13 L1311P,
1670 13
1661 0 G1661R, G1661R, G1661E,
1655 10
398 7
400 14 G400R, G400R, G400E, G400A,
1667 9 V1667I,
1664 4
1658 7