SCN5A Variant L917V

Summary of observed carriers, functional annotations, and structural context for SCN5A L917V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

30%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L917V 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 3 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 (%)
0.04 0.992 1.16 0.577 51 1

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 0 3 – –

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 L917V.
Neighbour residue Distance (Å) Observed variants
364 15
891 14 I891N, I891T,
856 13 V856L, V856L,
919 7
363 11
360 13
894 13 I894M,
254 14
926 15
925 12 I925F
904 13 W904X,
366 12
258 15 V258A,
221 14
924 11 V924I,
857 13 G857D,
902 13
921 6
922 10 V922I,
362 12
860 11 p.L860fsx89,
911 12 G911E,
920 5
900 13
918 5
917 0 L917V, L917R,
913 8
916 4
912 10 Q912R,
906 11
910 12 S910L,
903 9 p.M903CfsX29,
359 13 A359T, p.A359PfsX12,
853 12
923 11
352 15 Y352C,
915 7 C915R,
899 11
914 6
861 11 p.F861WfsX90, c.2582_2583delTT,
220 14 T220I,
907 10