SCN5A Variant F366L

Summary of observed carriers, functional annotations, and structural context for SCN5A F366L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

46%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F366L 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 0.915 67 12

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 – 0 0 0 0 –
Variant features alone – 15 11 0 4 – –

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 F366L.
Neighbour residue Distance (Å) Observed variants
403 15
364 7
266 15 L266H,
919 12
363 6
404 10 L404V, L404Q,
360 12
396 10 V396L, V396A,
894 13 I894M,
355 13 F355I, F355C,
254 11
372 9
401 9 S401P,
926 14
371 10 Q371E,
250 15
928 11 L928P
925 14 I925F,
361 10
904 13 W904X,
260 11
366 0
365 6
258 10 V258A,
354 14
897 11 G897R, G897R, G897E,
924 10 V924I,
927 12 N927S, N927K, N927K,
369 5 M369K,
902 14
402 14 F402L, F402L, F402L,
373 12
267 15
262 11 S262G,
898 13
256 13
921 12
922 12 V922I,
399 15
397 11 I397V, I397F, I397T,
405 11
261 7
362 6
920 7
900 10
392 14
255 14
918 14
393 14
917 12 L917V, L917R,
916 10
264 11
259 14
265 11 A265V,
408 13
253 14
374 12 W374G,
407 14
358 13
903 11 p.M903CfsX29,
367 7 R367C, R367H, R367L,
263 13 V263I,
359 11 A359T, p.A359PfsX12,
370 5 T370M,
923 9
352 15 Y352C,
406 14 N406S, N406K, N406K,
368 7
899 8
915 15 C915R,
268 14 G268S,
377 12
257 9
400 11 G400R, G400R, G400E, G400A,
353 13 T353I,
907 14