SCN5A Variant L377R

Summary of observed carriers, functional annotations, and structural context for SCN5A L377R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

9%

0/10 effective observations

Estimated BrS1 penetrance

29%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L377R 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 0.99 37 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 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 L377R.
Neighbour residue Distance (Å) Observed variants
364 7
277 14
271 14 L271V,
1702 13
901 13 E901K, S901L,
276 8 L276Q, L276P,
363 11
348 9 P348A,
360 13
396 11 V396L, V396A,
385 12 A385T,
355 9 F355I, F355C,
1687 14
391 15
278 14 H278D, H278R,
372 9
401 15 S401P,
356 14 D356N,
371 11 Q371E,
1711 11 c.5131delG,
361 11
904 12 W904X,
366 12
365 10
1706 10 Q1706H, Q1706H,
376 6 R376C, R376H,
384 11 S384T,
354 9
1692 13
386 12 G386R, G386R, G386E,
369 13 M369K,
378 7
349 10 D349N,
373 8
267 15
1712 13 G1712S, G1712C
379 7
1703 14
898 14
272 10
397 11 I397V, I397F, I397T,
274 13 G274C,
362 14
1709 13 p.T1709del, T1709R, T1709M,
325 11 L325R,
900 10
392 10
324 13
389 12 Y389H, Y389X,
269 14
395 15
393 8
394 14
390 13
275 12 N275K, N275K,
264 14
383 11
347 11
382 9
351 12 G351S, G351C, G351D, G351V,
265 13 A265V,
374 6 W374G,
1705 13
1689 15 D1689N,
350 13 H350Q, H350Q,
903 14 p.M903CfsX29,
367 6 R367C, R367H, R367L,
370 12 T370M,
381 6 c.1140+1G>A, c.1141-3C>A,
375 7
1691 14
352 13 Y352C,
368 7
899 12
1710 15 S1710L,
380 6
268 12 G268S,
377 0
1419 15 K1419E,
353 7 T353I,