SCN5A Variant L368M

Summary of observed carriers, functional annotations, and structural context for SCN5A L368M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

15%

0/10 effective observations

Estimated BrS1 penetrance

45%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L368M 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 0.845 66 17

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 L368M.
Neighbour residue Distance (Å) Observed variants
403 13
364 6
271 14 L271V,
266 14 L266H,
276 14 L276Q, L276P,
363 9
404 12 L404V, L404Q,
360 14
396 5 V396L, V396A,
355 10 F355I, F355C,
391 13
372 8
401 8 S401P,
371 6 Q371E,
1711 12 c.5131delG,
928 15 L928P,
361 10
904 14 W904X,
260 12
366 7
365 5
1706 12 Q1706H, Q1706H,
376 12 R376C, R376H,
258 14 V258A,
354 13
897 13 G897R, G897R, G897E,
369 6 M369K,
378 10
402 11 F402L, F402L, F402L,
373 9
267 12
1712 15 G1712S, G1712C
379 13
262 13 S262G,
898 14
399 11
272 12
397 6 I397V, I397F, I397T,
405 12
362 10
261 10
920 14
1709 10 p.T1709del, T1709R, T1709M,
900 11
392 8
389 14 Y389H, Y389X,
269 14
395 10
393 7
390 13
394 11
264 9
1708 14 T1708I,
382 14
265 10 A265V,
374 6 W374G,
1705 12
358 14
903 15 p.M903CfsX29,
367 5 R367C, R367H, R367L,
263 13 V263I,
359 14 A359T, p.A359PfsX12,
370 7 T370M,
381 11 c.1140+1G>A, c.1141-3C>A,
923 14
375 11
406 15 N406S, N406K, N406K,
368 0
899 11
380 13
1710 13 S1710L,
268 11 G268S,
377 7
398 12
257 13
400 9 G400R, G400R, G400E, G400A,
353 12 T353I,