SCN5A Variant Y339N

Summary of observed carriers, functional annotations, and structural context for SCN5A Y339N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

29%

1/10 effective observations

Estimated BrS1 penetrance

18%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y339N has not been reported in gnomAD. This residue resides in a Mild_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 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 0.889 18 37

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 1 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 Y339N.
Neighbour residue Distance (Å) Observed variants
328 14
333 13 c.998+1G>A, c.998+5G>A,
341 10 C341Y,
342 10
326 9
335 7 C335R, C335S,
327 11
339 0
319 12 G319C, G319R, G319S,
325 13 L325R,
284 9
336 4 P336L,
282 5 R282H, R282C,
279 11
324 11
321 13 S321Y
344 14 A344S,
340 7 R340W, R340Q,
338 4
285 11 T285K,
322 14
278 14 H278D, H278R,
334 10 c.999-424_1338+81del,
383 14
280 6 C280Y,
281 6 V281M,
323 11
283 7
337 7
286 12 A286S, A286V,
320 12 T320N,