SCN5A Variant G351C

Summary of observed carriers, functional annotations, and structural context for SCN5A G351C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

54%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

G351C has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
-7.79 1 -3.79 0.973 70 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
29325976 2018 1 0 1 0
Literature, cohort, and gnomAD 1 0 0 1
Variant features alone 15 11 0 4

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)
29325976 2018

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 G351C.
Neighbour residue Distance (Å) Observed variants
364 12
277 9
901 13 S901L, E901K,
276 10 L276P, L276Q,
363 11
348 6 P348A,
360 8
279 12
355 11 F355I, F355C,
1549 15
278 14 H278D, H278R,
356 10 D356N,
361 12
904 8 W904X,
343 14
376 12 R376H, R376C,
871 13
354 7
909 14
902 15
349 7 D349N,
1550 13
357 11
911 13 G911E,
272 15
274 12 G274C,
273 15
325 13 L325R,
900 12
324 14
321 13 S321Y,
872 13 D872N,
345 9
916 14
275 14 N275K, N275K,
912 10 Q912R,
323 13
347 4
906 14
351 0 G351C, G351V, G351S, G351D,
910 15 S910L,
350 5 H350Q, H350Q,
903 12 p.M903CfsX29,
367 13 R367L, R367C, R367H,
346 6 E346K, E346G, E346D, E346D, E346X,
359 12 p.A359PfsX12, A359T,
344 12 A344S,
381 15 c.1140+1G>A, c.1141-3C>A,
322 11
905 12
352 4 Y352C,
915 15 C915R,
380 12
377 12
908 10
353 5 T353I,
907 10