SCN5A Variant N347H

Summary of observed carriers, functional annotations, and structural context for SCN5A N347H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/10 effective observations

Estimated BrS1 penetrance

26%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

N347H 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 2 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 0.946 32 2

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 13 0 2

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 N347H.
Neighbour residue Distance (Å) Observed variants
364 12
277 6
326 14
276 7 L276Q, L276P,
363 13
348 4 P348A,
317 15 K317E, K317M, K317N, K317N,
360 10
279 9
355 10 F355I, F355C,
1549 14
278 10 H278D, H278R,
356 9 D356N,
361 12
904 10 W904X,
343 11
376 12 R376C, R376H,
384 12 S384T,
354 6
349 7 D349N,
1550 11
357 12
272 13
341 15 C341Y,
274 9 G274C,
273 13
325 10 L325R,
900 14
324 12
321 11 S321Y,
269 14
872 15 D872N,
345 7
275 11 N275K, N275K,
383 14
280 14 C280Y,
912 14 Q912R,
323 10
347 0
351 4 G351S, G351C, G351D, G351V,
320 13 T320N,
350 8 H350Q, H350Q,
903 15 p.M903CfsX29,
342 13
367 14 R367C, R367H, R367L,
1551 15 D1551N, D1551Y
346 5 E346K, E346G, E346X, E346D, E346D,
359 13 A359T, p.A359PfsX12,
344 9 A344S,
381 12 c.1140+1G>A, c.1141-3C>A,
322 9
905 15
352 7 Y352C,
380 10
268 15 G268S,
377 11
908 13
281 15 V281M,
353 5 T353I,
907 14