SCN5A Variant F393Y

Summary of observed carriers, functional annotations, and structural context for SCN5A F393Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

20%

1/10 effective observations

Estimated BrS1 penetrance

33%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F393Y 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 3 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 (%)
NA NA NA 0.954 44 23

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 1 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 F393Y.
Neighbour residue Distance (Å) Observed variants
364 11
271 11 L271V,
1702 10
266 15 L266H,
276 12 L276Q, L276P,
363 15
387 11
396 6 V396L, V396A,
385 11 A385T,
1624 15 V1624I,
355 11 F355I, F355C,
391 7
372 13
401 11 S401P,
388 10 I388S,
1698 14 A1698T,
371 10 Q371E,
1711 13 c.5131delG
361 13
332 15 A332T,
366 14
1707 14
365 9
1704 14 L1704H,
1706 10 Q1706H, Q1706H,
376 13 R376C, R376H,
384 13 S384T,
354 14
1668 15 M1668T,
1692 13
386 10 G386R, G386R, G386E,
369 11 M369K,
378 6
1699 15
402 12 F402L, F402L, F402L,
373 13
267 11
379 11
1703 13
399 11
272 10
397 7 I397V, I397F, I397T,
261 14
1709 11 p.T1709del, T1709R, T1709M,
1701 13 M1701I, M1701I, M1701I,
392 4
389 8 Y389H, Y389X,
269 14
395 8
393 0
390 7
394 6
275 14 N275K, N275K,
383 14
264 10
1708 13 T1708I,
382 8
265 12 A265V,
374 7 W374G,
1705 8
367 11 R367C, R367H, R367L,
263 14 V263I,
370 13 T370M,
381 8 c.1140+1G>A, c.1141-3C>A,
375 11
1691 15
368 7
380 11
1710 15 S1710L,
268 10 G268S,
377 8
398 11
400 11 G400R, G400R, G400E, G400A,
353 14 T353I,