SCN5A Variant N291K

Summary of observed carriers, functional annotations, and structural context for SCN5A N291K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

13%

0/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

N291K is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-1.84 0.929 -1.21 0.595 7 19

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 – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

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 N291K.
Neighbour residue Distance (Å) Observed variants
276 15 L276Q, L276P,
277 14
278 14 H278R, H278D,
279 13
280 13 C280Y,
281 12 V281M,
282 11 R282H, R282C,
283 11
284 10
285 9 T285K,
286 8 A286S, A286V,
287 8
288 7 N288S,
289 5 G289S,
290 4 p.T290_G292del,
291 0 N291S, N291H, p.N291_S293dup, N291K, p.N291TfsX52, N291K,
292 4 G292S,
293 5
294 7 V294M,
295 8 E295K,
296 8
297 9
298 10 G298S, G298D,
299 11 L299F, L299M, L299F,
300 11 V300I,
301 12
302 13
303 13
304 14
305 14 D305N
306 15 L306F, L306V,