SCN5A Variant A364E

Summary of observed carriers, functional annotations, and structural context for SCN5A A364E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

40%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

A364E 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 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 0.753 58 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 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 A364E.
Neighbour residue Distance (Å) Observed variants
364 0
277 15
271 13 L271V,
266 12 L266H,
919 15
901 14 S901L, E901K,
276 11 L276Q, L276P,
363 4
348 12 P348A,
270 15 Q270K,
360 8
396 10 V396L, V396A,
355 6 F355C, F355I,
372 9
401 13 S401P,
356 11 D356N,
371 11 Q371E,
361 5
904 10 W904X
260 14
366 7
365 5
376 12 R376C, R376H,
258 14 V258A,
354 8
897 14 G897R, G897E, G897R,
1546 15 M1546T,
369 9 M369K,
378 13
902 15
349 12 D349N,
373 11
267 12
379 15
262 12 S262G,
357 11
898 15
272 11
397 12 I397F, I397T, I397V,
274 14 G274C,
362 7
261 9
273 14
920 12
900 9
392 11
269 11
395 14
393 11
917 15 L917V, L917R,
916 12
275 14 N275K, N275K,
264 11
912 14 Q912R,
347 12
351 12 G351S, G351V, G351C, G351D,
265 8 A265V,
374 10 W374G,
350 13 H350Q, H350Q,
358 10
903 11 p.M903CfsX29,
367 5 R367L, R367C, R367H,
263 13 V263I,
359 9 A359T, p.A359PfsX12,
370 10 T370M,
381 12 c.1140+1G>A, c.1141-3C>A,
923 14
375 13
352 10 Y352C,
368 6
899 10
380 12
268 9 G268S,
377 7
257 14
400 13 G400R, G400R, G400E, G400A,
353 7 T353I,
907 13