SCN5A Variant A344E

Summary of observed carriers, functional annotations, and structural context for SCN5A A344E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/10 effective observations

Estimated BrS1 penetrance

14%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

A344E has not been reported 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 1 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 0.693 13 7

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 14 0 1

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 A344E.
Neighbour residue Distance (Å) Observed variants
328 15
277 5
326 12
276 10 L276Q, L276P,
348 10 P348A,
317 8 K317E, K317M, K317N, K317N,
279 5
1549 15
278 7 H278D, H278R,
356 12 D356N,
318 13
343 5
327 12
339 14
384 12 S384T,
354 12
282 14 R282C, R282H,
340 12 R340W, R340Q,
349 14 D349N,
283 14
1550 10
341 9 C341Y,
274 9 G274C,
273 13
319 11 G319S, G319R, G319C,
325 10 L325R,
324 13
321 9 S321Y,
345 3
275 10 N275K, N275K,
280 10 C280Y,
323 10
347 9
351 12 G351S, G351C, G351D, G351V,
320 8 T320N,
342 6
1551 11 D1551N, D1551Y
346 7 E346K, E346G, E346X, E346D, E346D,
344 0 A344S,
322 11
352 15 Y352C,
380 14
281 8 V281M,
353 13 T353I,