SCN5A Variant F1775V

Summary of observed carriers, functional annotations, and structural context for SCN5A F1775V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

27%

1/11 effective observations

Estimated BrS1 penetrance

19%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

F1775V 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 2 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-6.47 0.952 -2.62 0.966 20 40

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 1 2

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 F1775V.
Neighbour residue Distance (Å) Observed variants
403 12
414 7 M414V,
939 14 L939F,
1785 15
1643 11 I1643L,
404 12 L404V, L404Q,
1778 6
1773 8
249 11 K249X,
1653 10
254 15
1771 7 I1771T,
1652 9 M1652T, M1652R,
1777 7 V1777M, V1777L, V1777L,
418 13 E418K,
250 12
409 9 L409V, L409P,
1650 8 L1650F,
1656 15
1641 14
417 13
1477 14 K1477N, K1477N,
246 13
1779 6 T1779M,
412 10 V412D,
935 15 L935P,
1493 14 p.K1493del, K1493X, K1493R,
1470 13
245 15 Q245K,
1776 5
1787 13 S1787N,
1767 14 Y1767C,
1654 14
1648 10
1769 11
415 11 A415T,
1649 6 A1649V,
1768 12 I1768V,
1774 7 N1774D, c.5321_5324dupACTT,
1473 14 F1473S, F1473C,
1644 13 R1644C, R1644H, R1644L,
256 14
405 13
1657 14
1474 13
1781 10 E1781G, E1781D, E1781D,
1772 6 L1772V,
1645 8 T1645M,
251 15
410 5 A410V,
1780 9 E1780G,
1788 14 c.5361_5364delTGAG
1770 11 I1770V,
1651 12
416 15 Y416C,
413 9 A413T, A413E,
408 10
253 11
407 7
1783 12
936 14
1775 0 F1775V, p.F1775LfsX15,
1642 10 G1642E,
406 10 N406S, N406K, N406K,
252 13
411 7 V411M,
932 14
1647 10
1646 6
1489 15 E1489D, E1489D,
1782 10