SCN5A Variant A1680P

Summary of observed carriers, functional annotations, and structural context for SCN5A A1680P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

16%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

A1680P is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_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 (%)
-3.58 0.984 -1.98 0.826 18 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 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 A1680P.
Neighbour residue Distance (Å) Observed variants
1741 8 D1741N, D1741Y, D1741E, D1741E,
1304 15 T1304M,
1687 15
1698 14 A1698T,
1745 13
1673 12
1675 8
1743 9 G1743R, G1743R, G1743E,
1681 5 c.5040_5042delTTAinsC, Y1681F,
1694 7
1226 8
1747 12 V1747M,
1716 14 p.L1716SfsX71,
1695 6 Q1695X,
1688 11
1684 12 W1684R, W1684R,
1676 7 M1676T, M1676I, M1676I, M1676I,
1692 14
1744 10 S1744I,
1721 14
1672 12 S1672Y,
1742 9
1693 8
1699 12
1738 13 S1738T, S1738F,
1680 0 A1680T, A1680P,
1703 13
1719 12
1731 14
1228 12 Y1228H, Y1228C, Y1228F,
1690 12 c.5068_5070delGA, D1690N,
1678 7 N1678S,
1223 15 c.3667delG,
1697 13
1230 14 E1230K,
1227 7
1300 13
1674 12 F1674V,
1229 13
1748 13 p.G1748del, G1748D
1683 9
1301 13
1696 10
1689 15 D1689N,
1739 11 R1739W, R1739Q,
1700 11
1717 15 L1717P,
1734 14
1751 13
1677 7
1682 5
1752 15
1722 14 N1722D,
1740 7 G1740R, G1740R,
1225 12 E1225K, G1225K,
1691 15
1720 10 c.5157delC,
1732 11
1679 6
1685 14