SCN5A Variant L895F

Summary of observed carriers, functional annotations, and structural context for SCN5A L895F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

21%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L895F 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 2 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 (%)
-3.83 0.005 -0.82 0.89 29 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 – 1 1 0 0 –
Variant features alone – 15 13 0 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 L895F.
Neighbour residue Distance (Å) Observed variants
891 7 I891N, I891T,
848 13 I848F,
890 10 I890T,
901 15 E901K, S901L,
919 11
896 4 C896S, C896S,
895 0 L895F,
1417 14
842 13
894 5 I894M,
1457 13
1453 14
1455 11
1447 14
372 12
1452 14
926 5
371 15 Q371E,
928 10 L928P,
1450 14
925 9 I925F,
887 12
1451 11 V1451L, V1451D,
934 12
1458 11 S1458Y,
933 13
935 13 L935P,
851 13 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 7 G897R, G897R, G897E,
924 10 V924I,
927 6 N927S, N927K, N927K,
852 13
854 12 c.2559delT,
845 12 c.2533delG,
1422 13 M1422R,
1418 10
902 13
892 5 F892I,
373 15
849 9
888 10
898 9
893 8 R893C, R893H,
921 12
922 7 V922I,
405 14
1462 14
920 12
889 10
843 12 T843A,
900 14
1456 15
930 8 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 8 c.4376_4379delTCTT,
918 13
1425 15
1454 10
929 10
1448 15 I1448L, I1448T,
408 15
1421 12
847 10
846 8 L846R,
903 14 p.M903CfsX29,
1416 13 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
853 10
370 12 T370M,
879 14 W879R, W879R,
923 7
899 11
1415 14
844 15 L844RfsX3,
850 8 V850M, c.2549_2550insTG,
243 15
932 11
1419 14 K1419E,
931 7
1463 13 N1463Y