SCN5A Variant D305N

Summary of observed carriers, functional annotations, and structural context for SCN5A D305N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/12 effective observations

Estimated BrS1 penetrance

5%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

D305N is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-0.97 0.801 -0.11 0.381 4 0

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 – 2 2 0 0 –
Variant features alone – 15 15 0 0 – –

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 D305N.
Neighbour residue Distance (Å) Observed variants
290 15 p.T290_G292del,
291 14 N291S, p.N291TfsX52, N291K, p.N291_S293dup, N291H, N291K
292 14 G292S,
293 13
294 13 V294M,
295 12 E295K,
296 11
297 11
298 10 G298S, G298D,
299 9 L299M, L299F, L299F,
300 8 V300I,
301 8
302 7
303 5
304 4
305 0 D305N,
306 4 L306F, L306V,
307 5
308 7
309 8 S309N, S309C,
310 8 D310N,
311 9
312 10 E312K, c.934+4C>T, c.934+1G>A,
313 11
314 11
315 12 L315P,
316 13
317 13 K317M, K317N, K317N, K317E,
318 14
319 14 G319R, G319S, G319C,
320 15 T320N,