SCN5A Variant L299M

Summary of observed carriers, functional annotations, and structural context for SCN5A L299M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/70 effective observations

Estimated BrS1 penetrance

1%

0/70 effective observations

Total carriers

60

0 BrS1 · 0 LQT3 · 60 unaffected

L299M is present in 59 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 (%)
0.05 0.008 -1.05 0.308 5 1

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
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 60 60 0 0 –
Variant features alone – 15 15 0 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
20129283 2010
32533946 2020 HEK 104 5.2 2.6

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 L299M.
Neighbour residue Distance (Å) Observed variants
284 15
285 14 T285K,
286 14 A286S, A286V,
287 13
288 13 N288S,
289 12 G289S,
290 11 p.T290_G292del,
291 11 N291K, p.N291TfsX52, p.N291_S293dup, N291S, N291K, N291H,
292 10 G292S,
293 9
294 8 V294M,
295 8 E295K,
296 7
297 5
298 4 G298S, G298D,
299 0 L299F, L299M, L299F,
300 4 V300I,
301 5
302 7
303 8
304 8
305 9 D305N,
306 10 L306F, L306V,
307 11
308 11
309 12 S309C, S309N,
310 13 D310N,
311 13
312 14 c.934+1G>A, c.934+4C>T, E312K,
313 14
314 15