SCN5A Variant p.L860fsx89

Summary of observed carriers, functional annotations, and structural context for SCN5A p.L860fsx89. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

52%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

p.L860fsx89 has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_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 (%)
NA NA NA None 69 14

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
16764707 2006 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)
16764707 2006

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 p.L860fsx89.
Neighbour residue Distance (Å) Observed variants
891 13 I891N, I891T,
880 14
223 11 V223L,
856 6 V856L, V856L,
890 13 I890T,
919 11
862 7
867 13 E867K, E867Q, E867X,
859 5
863 9
887 12
864 9
216 8 S216X, S216L,
851 14 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 9
909 12
852 12
854 10 c.2559delT,
222 13 R222X, R222Q, R222L,
224 13 L224F,
857 5 G857D,
902 14
882 12
881 9
921 13
922 14 V922I
860 0 p.L860fsx89,
911 12 G911E,
920 15
214 14
858 8 M858L, M858L,
217 8
918 8
855 9
917 11 L917V, L917R,
865 11
913 9
916 13
148 14
912 14 Q912R,
884 14
906 10
866 14 S866P, S866L,
910 9 S910L,
203 14
903 14 p.M903CfsX29,
853 11
219 10 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
151 15
218 11
883 14
905 15
915 8 C915R,
215 10 p.L215CfsX10,
850 15 V850M, c.2549_2550insTG,
914 6
861 4 p.F861WfsX90, c.2582_2583delTT,
220 6 T220I,
907 13