SCN5A Variant R1638Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R1638Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/12 effective observations

Estimated BrS1 penetrance

8%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

R1638Q is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-2.18 1 0.13 0.785 7 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
Literature, cohort, and gnomAD 2 2 0 0
Variant features alone 15 15 0 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 R1638Q.
Neighbour residue Distance (Å) Observed variants
1794 14
1643 11 I1643L,
1795 15 Y1795N, Y1795H, p.Y1795_E1796insD, Y1795C,
1531 12
1635 8
1634 10 L1634P,
1820 14 A1820T, A1820V,
1641 8
1639 6 G1639A,
1787 12 S1787N,
1648 12
1532 13 V1532I, V1532F,
1821 14
1644 6 R1644C, R1644H, R1644L,
1640 9
1797 12 I1797V,
1800 14
1793 8 M1793K,
1789 7
1632 14 R1632C, R1632H, R1632L,
1645 11 T1645M,
1796 9
1535 14
1799 15
1788 12 c.5361_5364delTGAG,
1638 0 R1638X, R1638Q,
1651 14
1633 11
1791 14
1637 6
1792 9 D1792N, D1792Y, D1792V,
1636 7
1823 14 E1823K, p.E1823HfsX10
1642 11 G1642E,
1528 11
1790 11 D1790N, D1790G, p.D1790del,
1631 14 G1631D,
252 15
1647 11
1822 11 c.5464_5467delTCTG, c.5464-5467delTCTG,
1646 14