SCN5A Variant K343M

Summary of observed carriers, functional annotations, and structural context for SCN5A K343M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

0/10 effective observations

Estimated BrS1 penetrance

18%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

K343M 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 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 0.894 17 21

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 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 K343M.
Neighbour residue Distance (Å) Observed variants
328 12
277 5
271 14 L271V,
326 13
276 9 L276P, L276Q,
348 13 P348A,
317 12 K317N, K317N, K317E, K317M,
270 15 Q270K,
279 8
385 13 A385T,
1552 14 Q1552L, Q1552R,
355 14 F355I, F355C,
1549 12
278 6 H278D, H278R,
356 11 D356N,
343 0
327 11
384 11 S384T,
354 12
340 12 R340Q, R340W,
1550 7
357 15
272 12
341 8 C341Y,
274 6 G274C,
273 9
325 12 L325R,
321 14 S321Y,
269 14
345 8
275 8 N275K, N275K
280 12 C280Y,
323 13
347 11
351 14 G351C, G351V, G351S, G351D,
320 12 T320N,
342 6
1551 8 D1551N, D1551Y,
346 11 E346G, E346D, E346K, E346X, E346D,
344 5 A344S,
381 14 c.1141-3C>A, c.1140+1G>A,
380 15
281 11 V281M,
353 14 T353I,