SCN5A Variant L365H

Summary of observed carriers, functional annotations, and structural context for SCN5A L365H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

13%

0/10 effective observations

Estimated BrS1 penetrance

44%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L365H 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 0.971 63 13

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 L365H.
Neighbour residue Distance (Å) Observed variants
403 15
364 5
271 13 L271V,
266 10 L266H,
276 14 L276Q, L276P,
363 7
404 12 L404Q, L404V,
270 14 Q270K,
360 11
1627 15
396 7 V396A, V396L,
355 8 F355I, F355C,
391 15
254 14
372 11
401 10 S401P,
356 13 D356N,
371 11 Q371E,
361 6
904 14 W904X,
260 9
366 6
365 0
258 11 V258A,
354 11
1546 13 M1546T,
369 6 M369K,
378 13
402 14 F402L, F402L, F402L,
373 13
267 9
262 9 S262G,
357 12
256 14
399 12
272 11
397 9 I397V, I397T, I397F,
405 14
362 6
261 6
273 15
920 13
900 12
392 9
389 14 Y389X, Y389H,
269 11
395 11
393 9
916 14
394 13
264 7
259 12
265 6 A265V,
374 11 W374G,
358 10
903 14 p.M903CfsX29,
367 7 R367H, R367L, R367C,
263 9 V263I,
359 10 A359T, p.A359PfsX12,
370 9 T370M,
381 13 c.1141-3C>A, c.1140+1G>A,
923 14
368 5
899 12
352 15 Y352C,
380 15
268 8 G268S,
377 10
398 14
257 11
400 10 G400E, G400A, G400R, G400R,
353 11 T353I,