SCN5A Variant L395R

Summary of observed carriers, functional annotations, and structural context for SCN5A L395R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

22%

1/10 effective observations

Estimated BrS1 penetrance

40%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L395R 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 3 individuals for Brugada syndrome and 1 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 0.965 56 26

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 1 3

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 L395R.
Neighbour residue Distance (Å) Observed variants
403 11
364 14
271 12 L271V,
266 13 L266H,
404 13 L404V, L404Q,
1627 12
396 5 V396L, V396A,
1624 11 V1624I,
355 14 F355I, F355C,
391 6
388 12 I388S,
401 11 S401P,
371 13 Q371E,
260 11
365 11
386 15 G386R, G386R, G386E,
369 11 M369K,
1767 14 Y1767C
378 13
1654 13
402 11 F402L, F402L, F402L,
1630 15 I1630V, I1630R,
267 9
1625 14
262 13 S262G,
399 5
272 13
397 7 I397V, I397F, I397T,
1657 14
261 12
1709 15 p.T1709del, T1709R, T1709M,
1628 12
392 6
389 11 Y389H, Y389X,
1620 15 T1620K, T1620M,
395 0
393 8
390 9
394 5
264 7
259 14
382 15
265 12 A265V,
374 13 W374G,
1705 12
263 10 V263I,
1661 13 G1661R, G1661R, G1661E,
381 14 c.1140+1G>A, c.1141-3C>A,
368 10
1631 14 G1631D,
268 11 G268S,
377 15
398 7
257 15
400 8 G400R, G400R, G400E, G400A,
1621 14
1664 14
1658 12